Histone Deacetylase 1 (HDAC1) – Function, Mechanisms, and Roles in Mouse Biology

Overview and Enzymatic Function

Histone deacetylase 1 (HDAC1) is a zinc-dependent metalloenzyme involved in epigenetic regulation. It catalyzes the removal of acetyl groups from ε-N-acetyl lysine residues on histone proteins, producing deacetylated lysine and acetate (enzyme.expasy.org) (enzyme.expasy.org). By reversing the acetylation of histone tails (a modification associated with open chromatin), HDAC1 promotes chromatin compaction and transcriptional repression. HDAC1 is evolutionarily conserved (the mammalian homolog of yeast Rpd3) and can also deacetylate certain non-histone proteins involved in gene expression (www.degruyterbrill.com). This enzyme is classified as EC 3.5.1.98 (histone deacetylase), reflecting its amidohydrolase activity on N^6^-acetyl-lysine groups (enzyme.expasy.org).

Biochemically, HDAC1 belongs to Class I HDACs, which also includes HDAC2, HDAC3, and HDAC8 (pmc.ncbi.nlm.nih.gov). Class I HDACs are ubiquitously expressed and predominantly nuclear enzymes (pmc.ncbi.nlm.nih.gov). HDAC1 requires a Zn^2+ cofactor at its active site for catalysis and operates via a charge-relay mechanism to hydrolyze the amide bond of acetyl-lysine. The net reaction removes the acetyl group from histone lysines (e.g. on H3 and H4 tails), opposing the activity of histone acetyltransferases (HATs) (enzyme.expasy.org). This deacetylation generally causes the DNA to wrap more tightly around nucleosomes, limiting access of transcription factors and thereby downregulating gene expression (pmc.ncbi.nlm.nih.gov). Notably, HDAC1 shows broad substrate specificity for acetylated lysines on core histones; recent high-resolution studies indicate HDAC1 regulates the majority of acetylation sites on core histones, with certain lysines on H2B being especially sensitive to HDAC1 loss (academic.oup.com).

In addition to classical deacetylation, new research (2023) has revealed that HDAC1 (together with its close paralogs HDAC2 and HDAC3) can act on other acyl modifications such as lysine succinylation. While lysine succinylation was previously thought to be removed mainly by NAD^+^-dependent sirtuins, a 2023 study showed that class I HDACs, particularly HDAC1/2/3, are the principal histone desuccinylases in mammalian cells (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Inhibiting or knocking down HDAC1/2/3 caused a marked increase in global histone succinylation, whereas ectopic expression of active HDAC1/2/3 reduced succinylation levels (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This finding expands the functional repertoire of HDAC1 beyond deacetylation, suggesting it can remove larger acyl groups (like succinyl) from lysines, thereby influencing chromatin structure and gene activity in additional ways.

Cellular Localization and Complexes

HDAC1 is predominantly a nuclear protein, consistent with its role in modifying chromatin. It is enriched in the nucleus and often associated with heterochromatin regions (www.ncbi.nlm.nih.gov). Within the nucleus, HDAC1 does not typically act alone; instead, it functions as part of multi-protein complexes that target it to specific genes. In cells, HDAC1 and the closely related HDAC2 usually form a heterodimer that serves as the catalytic core of several large co-repressor complexes (pmc.ncbi.nlm.nih.gov). Major HDAC1-containing complexes include:

• SIN3A complex – scaffolded by the Sin3 adaptor protein
• NuRD complex (nucleosome remodeling and deacetylase) – containing Mi-2/CHD4, MTA proteins, RbAp46/48, etc.
• CoREST complex – associated with the CoREST/LSD1 repressor for neuron-specific genes
• Other less abundant HDAC1 complexes (e.g. MiDAC, MIER, and RERE complexes) identified in various contexts (pmc.ncbi.nlm.nih.gov).

Proteomic analysis in mouse embryonic stem cells (ESCs) showed that the vast majority of HDAC1 is sequestered in a few complexes. Strikingly, ~92% of cellular HDAC1 in ESCs was found in just three complexes: about 49% in the NuRD complex, 28% in CoREST, and 15% in SIN3A, with only a minor fraction unbound or in smaller assemblies (pmc.ncbi.nlm.nih.gov). This underscores that HDAC1’s in vivo function is tightly linked to these co-repressor complexes, which provide targeting specificity. The adapter proteins in each complex recruit HDAC1 to particular genomic sites – for example, SIN3A complexes bind DNA through sequence-specific repressors, and NuRD can be recruited via methylated DNA or transcription factors (pmc.ncbi.nlm.nih.gov). HDAC1/2 serve not only as catalytic subunits in these complexes but also as structural components stabilizing complex assembly (pmc.ncbi.nlm.nih.gov).

Because of the critical role of these interactions, specific surface residues on HDAC1 mediate its binding to different complex proteins. A recent 2025 structure-function study demonstrated that mutating a single amino acid on HDAC1’s surface (Tyr48) disrupted its incorporation into most complexes except SIN3, highlighting how distinct interfaces on HDAC1 are required for complex-specific interactions (pmc.ncbi.nlm.nih.gov). This kind of evidence shows that HDAC1’s function and regulation depend on its partners, and disrupting those partnerships can profoundly alter which genes HDAC1 can target.

Biological Roles and Processes

HDAC1 is a global regulator of gene expression with widespread effects on cell fate, proliferation, and development. By deacetylating histones, HDAC1 generally represses transcription, and it plays a key role in maintaining the balance between gene activation and silencing in many pathways. Gene ontology annotations and experimental studies indicate HDAC1 is involved in numerous biological processes:

• Embryonic Development: HDAC1 is essential for early development. Mouse embryos completely lacking Hdac1 die during early embryogenesis, reflecting severe proliferation and differentiation defects. In early blastocysts, HDAC1 and HDAC2 have redundant roles – only when both are disrupted do embryos fail to form a proper blastocyst, with increased apoptosis linked to hyperacetylation of p53 (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). However, later in development and in specific lineages, HDAC1 has unique, non-redundant functions. For example, in the developing brain, HDAC1 is somewhat more critical than HDAC2: one study found that a single copy of Hdac2 could not fully rescue brain development if Hdac1 was completely knocked out, indicating Hdac1 provides functions that Hdac2 cannot wholly compensate (pubmed.ncbi.nlm.nih.gov). Conversely, a single Hdac1 allele was more capable of offsetting the loss of Hdac2, underscoring the dominant role of HDAC1 in neurodevelopment (pubmed.ncbi.nlm.nih.gov).

• Neurogenesis and Differentiation: HDAC1 is highly expressed in the nervous system and influences neural progenitor differentiation. It is required for proper nervous system development and has been linked to specific events like oligodendrocyte maturation (www.ncbi.nlm.nih.gov). A recent study (Zhu et al., 2024) showed that HDAC1 (together with HDAC2) regulates the transition of neural stem cells during cortex development by restraining Wnt signaling (pmc.ncbi.nlm.nih.gov). Conditional deletion of Hdac1/2 in early neuroepithelial progenitors led to aberrant activation of Wnt-target genes, which in turn blocked the normal progression of these progenitors into radial glial cells and caused cortical architectural defects (pmc.ncbi.nlm.nih.gov). This finding illustrates a precise role: HDAC1/2-mediated deacetylation keeps Wnt pathway genes in check during neurogenesis. In line with this, administering a Wnt inhibitor could partially rescue the neurodevelopmental defects caused by HDAC1/2 loss (pmc.ncbi.nlm.nih.gov). HDAC1 also supports the differentiation of glial cells – for instance, oligodendrocyte differentiation (formation of myelinating glia) is positively regulated by HDAC1 activity (www.ncbi.nlm.nih.gov), likely through repression of inhibitors of myelination. Consistent with these roles, neuronal survival and memory processes can be affected by HDAC1 levels: in aging and disease models, imbalanced Class I HDAC activity is linked to cognitive deficits, and HDAC inhibitors are being studied to modulate memory-related gene expression (pmc.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov) (Brain Res. 2024).

• Immune Cell Development: HDAC1 is also crucial in the hematopoietic and immune systems. A 2024 study demonstrated that HDAC1 controls the development of certain dendritic cell (DC) subsets and thereby influences immune responses (pubmed.ncbi.nlm.nih.gov). Mice lacking Hdac1 in early blood progenitors had severely reduced production of plasmacytoid dendritic cells (pDCs) and a subset of conventional DCs, while other lineages (like cDC1) were unaffected (pubmed.ncbi.nlm.nih.gov). Notably, deleting Hdac2 in the same context had little effect on DC development, highlighting a non-redundant requirement for HDAC1 in this lineage (pubmed.ncbi.nlm.nih.gov). The HDAC1-deficient DC progenitors showed abnormal gene expression and chromatin accessibility, indicating HDAC1’s deacetylase activity is needed to properly program the DC differentiation transcriptional network (pubmed.ncbi.nlm.nih.gov). In human cells as well, knocking down HDAC1 impaired DC differentiation (pubmed.ncbi.nlm.nih.gov). This specialized role in the immune system suggests HDAC1 helps enforce the epigenetic programs that generate functional immune cells, and loss of HDAC1 may weaken immune surveillance (the study also linked HDAC1-deficient DCs to poor anti-tumor immunity (pubmed.ncbi.nlm.nih.gov)).

• Cell Cycle and Proliferation: HDAC1 has long been known to interact with cell cycle regulators. It partners with the Retinoblastoma (Rb) tumor suppressor and E2F transcription factors to repress E2F-responsive genes during cell cycle exit (pmc.ncbi.nlm.nih.gov). In G₀/G₁ phase, Rb recruits HDAC1 (via Sin3 or NuRD complexes) to promoters of S-phase genes (cyclins, replication factors), leading to local histone H4 deacetylation and gene silencing (pubmed.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). This Rb–HDAC1–E2F complex is important for enforcing cell cycle checkpoints. When cells are stimulated to divide, Rb is inactivated, HDAC1 is released, histones become acetylated, and E2F target genes are activated. If HDAC1 is lost, cells show inappropriate expression of cell-cycle genes and often a failure to properly exit the cell cycle. Indeed, HDAC1-null mouse embryos exhibit proliferation defects and increased apoptosis in proliferative tissues (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov), partly due to misregulation of cell-cycle inhibitors and hyperactivation of p53. Thus, HDAC1 plays a pro-proliferative role by repressing anti-proliferative genes under normal conditions. Consistent with this, many cancers show HDAC1 overexpression as a strategy to silence tumor suppressor genes and promote uncontrolled growth (www.degruyterbrill.com).

• Gene Silencing and DNA Methylation: HDAC1 often works in concert with DNA methyltransferases and other epigenetic silencers. For example, in some contexts HDAC1 is part of a repressor complex with DNMT1 (maintenance DNA methyltransferase), Rb, and E2F, which together maintain methylation and deacetylation at tumor suppressor gene promoters (www.nature.com). HDAC1’s deacetylation can facilitate DNA methylation and vice versa, creating a repressive chromatin state. In cancer cells, simultaneous inhibition of HDAC1/2 and DNMTs synergistically reactivates silenced genes (pubmed.ncbi.nlm.nih.gov), underscoring that HDAC1 is a key executor of long-term gene silencing programs. HDAC1 is also located at heterochromatic regions like pericentromeres, where it helps maintain condensed, transcriptionally inactive chromatin (often in tandem with methyl-binding proteins and histone methyltransferases).

• Direct Regulation of Transcription Factors: Beyond chromatin-centric functions, HDAC1 can directly interact with and deacetylate several transcription factors, modulating their activity. For instance, the NF-κB family member RelA/p65 is acetylated in active states; HDAC1 binds to the Rel homology domain of p65 and deacetylates it, which attenuates NF-κB’s transcriptional activity (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). In a classic study, overexpression of HDAC1/2 was shown to repress NF-κB-dependent genes by this mechanism, and HDAC1–p65 interaction was required for turning off inflammatory gene expression after a stimulus (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Similarly, HDAC1 interacts with the muscle-specific transcription factor MyoD to repress muscle gene expression in undifferentiated cells (pmc.ncbi.nlm.nih.gov). Deacetylation of MyoD by HDAC1 keeps it in an inactive state until differentiation signals downregulate HDAC1, allowing MyoD to activate muscle genes. Another important target is the tumor suppressor p53: acetylation of p53 enhances its stability and activity, and HDAC1 (often in complex with MDM2 ubiquitin ligase) can deacetylate p53, leading to p53 inactivation and degradation (pubmed.ncbi.nlm.nih.gov). This HDAC1–p53 axis is one way that cells modulate apoptosis and DNA damage responses. In summary, HDAC1 influences several signaling pathways (Wnt, NF-κB, p53, MyoD, etc.) by deacetylating key factors or their histone targets, thereby integrating epigenetic control with cell signaling and fate decisions.

It is important to note that while HDAC1 is generally associated with transcriptional repression, its activity can sometimes positively influence gene expression in indirect ways. For example, an acute degradation study (2021, Nucleic Acids Res.) of HDAC1 in cells revealed an unexpected finding: for a subset of genes, removing HDAC1 caused reduced transcription, correlated with a loss of acetylation at certain super-enhancers (academic.oup.com). One explanation is that HDAC1 helps maintain a dynamic acetylation turnover at these regulatory regions; in its absence, aberrant hyperacetylation of certain factors or feedback mechanisms might lead to decreased net acetylation and gene activity (academic.oup.com). This nuance underscores that HDAC1’s role is context-dependent – while it is a repressor by nature, proper levels of HDAC1 activity are also required for normal activation of some genes (likely by preventing overshooting acetylation that could trigger compensatory shut-off). Nonetheless, the overarching role of HDAC1 is to enforce appropriate gene expression programs – shutting genes off when they should be silent and allowing activation when needed, in coordination with other chromatin modifiers.

Pathophysiology and Clinical Relevance

Given HDAC1’s fundamental role in regulating cell proliferation, differentiation, and survival, it is not surprising that its dysfunction is implicated in disease, especially cancer. HDAC1 is frequently overexpressed in tumors of diverse types (including breast, lung, and liver cancers), and high HDAC1 levels often correlate with poor patient prognosis (pmc.ncbi.nlm.nih.gov). By recruiting HDAC1, cancer cells can aberrantly silence tumor suppressor genes and DNA damage response genes. For example, overexpression of HDAC1 has been noted in aggressive subtypes of lung cancer and linked to increased metastasis and worse outcomes (pubmed.ncbi.nlm.nih.gov) (www.degruyterbrill.com). HDAC1 can also promote oncogenic traits by deacetylating and inactivating p53, as mentioned, which reduces apoptosis in cancer cells. In hepatocellular carcinoma (HCC) and other cancers, broad evidence shows that HDACs orchestrate multiple hallmarks of cancer – cell cycle progression, evasion of apoptosis, enhanced migration/invasion, metabolic rewiring – through their control of histone and non-histone acetylation (www.degruyterbrill.com). Consequently, HDAC1 has become a prominent therapeutic target in oncology.

HDAC Inhibitors (HDACi) are a class of epigenetic drugs designed to block the activity of HDAC1 and related enzymes. By inhibiting HDAC1, these drugs cause accumulation of acetylated histones, leading to reactivation of suppressed genes (such as those regulating cell cycle arrest or apoptosis in cancer cells). Several HDAC inhibitors have reached clinical use. The first FDA-approved HDAC inhibitor was Vorinostat (SAHA), approved in 2006 for cutaneous T-cell lymphoma; vorinostat inhibits Class I HDACs (including HDAC1) and causes growth arrest and cell death in cancer cells (pmc.ncbi.nlm.nih.gov). Since then, other HDAC1-targeting drugs have been approved: Romidepsin, a cyclic peptide that selectively targets HDAC1/2, is used for certain lymphomas; and the hydroxamate inhibitors Panobinostat and Belinostat were approved for multiple myeloma and T-cell lymphoma, respectively (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). (Panobinostat’s approval was later withdrawn in 2022 due to safety concerns (pmc.ncbi.nlm.nih.gov), but it demonstrated the potent effect of HDAC1/2 inhibition in refractory myeloma.) These inhibitors have shown efficacy in hematologic cancers by inducing apoptosis and cell-cycle arrest. However, their success in solid tumors has been limited when used alone (pmc.ncbi.nlm.nih.gov). As a result, HDAC inhibitors are often used in combination therapies – for example, HDAC1 blockade can sensitize tumors to other treatments. In one study, romidepsin (an HDAC1/2 inhibitor) not only killed biliary tract cancer cells but also enhanced their response to standard chemotherapy (cisplatin) (pmc.ncbi.nlm.nih.gov).

Beyond cancer, modulation of HDAC1 is being explored in neurodegenerative and psychiatric disorders. Because HDAC1 helps silence genes, HDAC inhibitors can potentially boost expression of neuroprotective or memory-related genes. Indeed, preclinical studies in mice suggest that inhibiting Class I HDACs can alleviate cognitive deficits caused by acute stress or in Alzheimer’s models (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). There is also interest in HDAC1 in aging and neurological diseases: for instance, HDAC1 dysfunction has been linked to DNA damage accumulation in neurons, and HDAC1 activation (in the correct context) might promote DNA repair in neurodegeneration (academic.oup.com). However, because HDAC1 is ubiquitously required, systemic inhibition carries risks (e.g. bone marrow suppression, GI toxicity). To minimize side effects, next-generation approaches include developing isoform-selective HDAC1/2 inhibitors or targeted HDAC1 degraders (PROTACs) (pmc.ncbi.nlm.nih.gov) that could degrade HDAC1 specifically in certain tissues or contexts. As of 2023, multiple Class I HDAC inhibitors selective for HDAC1-3 are in clinical trials for cancers and other diseases (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), and eight class I-selective agents were noted to be in trials ranging from Phase I to III (pmc.ncbi.nlm.nih.gov). The continued therapeutic interest underlines HDAC1’s importance: it is a double-edged sword – necessary for normal cell function but also a driver of pathology when misregulated.

Conclusion

HDAC1 (histone deacetylase 1) is a key epigenetic regulator in mice (and other mammals) that enforces transcriptional control by deacetylating histones and other proteins. It functions at the nexus of chromatin remodeling, cell cycle control, and developmental signaling. HDAC1 is mainly nuclear and acts within multi-unit co-repressor complexes (such as NuRD, SIN3A, and CoREST) that target it to specific genes (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov). Its primary biochemical activity is the removal of acetyl groups from histone lysines (enzyme.expasy.org), which leads to chromatin condensation and gene repression. This activity is critical for numerous processes: it helps progenitor cells exit the cell cycle and differentiate at the correct time, maintains stem cell pluripotency until differentiation cues arrive, and safeguards genome stability by regulating DNA repair genes and checkpoint proteins. HDAC1 is also adaptable – recent insights show it can erase other acyl modifications like succinylation (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov), reflecting a broader role in post-translational modification homeostasis.

At the organism level, HDAC1 is indispensable. Mice require HDAC1 for normal embryogenesis, as it supports proper lineage specification and prevents excess apoptotic cell death in early development (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov). In specialized cells, HDAC1 helps orchestrate developmental programs (neural differentiation via Wnt repression (pmc.ncbi.nlm.nih.gov), immune lineage commitment in dendritic cells (pubmed.ncbi.nlm.nih.gov), etc.) and maintains the silenced state of genes that should not be expressed (e.g. imprinted genes or tissue-specific genes in other cell types). When HDAC1 function is lost or imbalanced, cells typically exhibit aberrant gene expression – either unscheduled activation of genes or failure to activate others – leading to defects like developmental anomalies or cell death. This precise control is also exploited by diseases: cancer cells, for instance, often hijack HDAC1 to broadly repress anti-tumor pathways. As a result, HDAC1 has become a prominent drug target, and inhibiting its activity can reactivate latent gene expression programs to therapeutic benefit in cancer and possibly neurological disorders. Conversely, excessive HDAC1 inhibition can be detrimental, given its role in normal cell viability and identity.

In summary, HDAC1 serves as a molecular switch for gene regulation, working in chromatin complexes to ensure genes are turned “off” when they should be, but also enabling correct gene “on” states in response to developmental cues. Its importance is evident from both fundamental biology and translational medicine perspectives. Ongoing research (2023–2024) continues to uncover new facets of HDAC1 biology – from novel enzymatic capabilities (pmc.ncbi.nlm.nih.gov) to specific roles in complex diseases – solidifying HDAC1 as a central player in the epigenetic regulation of cell function and a critical link between the genome, chromatin state, and cellular phenotype.

References: (Key sources with publication year)

• HDAC1 catalytic activity and epigenetic function: Abdallah et al., 2023 – Epigenetics & Translational Medicine (pmc.ncbi.nlm.nih.gov); Expasy EC 3.5.1.98 entry (enzyme.expasy.org) (enzyme.expasy.org).
• HDAC1 class and complexes: Ashburner et al., 2001 – Mol. Cell. Biol. (pmc.ncbi.nlm.nih.gov); Alshehri et al., 2025 – Nucleic Acids Res. (pmc.ncbi.nlm.nih.gov).
• Biological processes (development, neurogenesis): Alliance of Genome Resources, 2025 – MGI/NCBI gene summary (www.ncbi.nlm.nih.gov); Zhu et al., 2024 – iScience (pmc.ncbi.nlm.nih.gov).
• Immune function: De Sá Fernandes et al., 2024 – Cell Reports (pubmed.ncbi.nlm.nih.gov).
• Transcription factor interactions: Ashburner et al., 2001 – Mol. Cell. Biol. (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov); Mal et al., 2001 – Mol. Cell (MyoD-HDAC1).
• HDAC1 in gene silencing: Robertson et al., 2000 – Nat. Genet. (HDAC1-Rb-DNMT1 complex); Cai et al., 2014 – Cancer Cell (NuRD & DNMT synergy) (pubmed.ncbi.nlm.nih.gov).
• Desuccinylase activity: Li et al., 2023 – Cell Discovery (pmc.ncbi.nlm.nih.gov) (pmc.ncbi.nlm.nih.gov).
• HDAC1 knockout phenotypes: Panpan Zhao et al., 2020 – Epigenetics (pubmed.ncbi.nlm.nih.gov) (pubmed.ncbi.nlm.nih.gov); Hagelkruys et al., 2014 – Development (Hdac1 vs Hdac2 in brain) (pubmed.ncbi.nlm.nih.gov).
• Cancer and clinical relevance: Xie et al., 2024 – Transl. Cancer Res. (pmc.ncbi.nlm.nih.gov); Zhang et al., 2025 – Oncologie (www.degruyterbrill.com); Vorinostat FDA approval, 2006 (pmc.ncbi.nlm.nih.gov); Patel et al., 2022 – Curr. Cancer Drug Targets (HDAC1 inhibitors).

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21. AnnotationURLCitation(end_index=9006, start_index=8838, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=role%20of%20histone%20modifications%20in,gene%20expression%20changes%2C%20a%20substantial')
22. AnnotationURLCitation(end_index=9134, start_index=9007, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=HDAC1%2F2,are%20core%20components%20of%20several')
23. AnnotationURLCitation(end_index=9649, start_index=9515, title='A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24449838/#:~:text=HDAC1%20and%20HDAC2%2C%20we%20expressed,brains%20showed')
24. AnnotationURLCitation(end_index=9929, start_index=9795, title='A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24449838/#:~:text=HDAC1%20and%20HDAC2%2C%20we%20expressed,brains%20showed')
25. AnnotationURLCitation(end_index=10343, start_index=10198, title='Hdac1 histone deacetylase 1 [Mus musculus (house mouse)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/433759#:~:text=upstream%20of%20or%20within%20several,Orthologous%20to%20human%20HDAC1')
26. AnnotationURLCitation(end_index=10714, start_index=10526, title='HDAC1 and HDAC2 orchestrate Wnt signaling to regulate neural progenitor transition during brain development - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11367519/#:~:text=neural%20differentiation%2C%20yet%20the%20governing,rescued%20the%20disrupted%20cortical%20architecture')
27. AnnotationURLCitation(end_index=11153, start_index=10965, title='HDAC1 and HDAC2 orchestrate Wnt signaling to regulate neural progenitor transition during brain development - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11367519/#:~:text=neural%20differentiation%2C%20yet%20the%20governing,rescued%20the%20disrupted%20cortical%20architecture')
28. AnnotationURLCitation(end_index=11587, start_index=11407, title='HDAC1 and HDAC2 orchestrate Wnt signaling to regulate neural progenitor transition during brain development - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11367519/#:~:text=signaling%20is%20essential%20for%20the,epigenetic%20mechanisms%20in%20neocortical%20development')
29. AnnotationURLCitation(end_index=11915, start_index=11770, title='Hdac1 histone deacetylase 1 [Mus musculus (house mouse)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/433759#:~:text=upstream%20of%20or%20within%20several,Orthologous%20to%20human%20HDAC1')
30. AnnotationURLCitation(end_index=12397, start_index=12254, title='Class 1 Histone Deacetylases Differentially Modulate Memory and Synaptic Genes in a Spatial and Temporal Manner in Aged and APP/PS1 Mice - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11182336/#:~:text=Class%201%20Histone%20Deacetylases%20Differentially,148951')
31. AnnotationURLCitation(end_index=12564, start_index=12398, title='Class 1 histone deacetylases differentially modulate memory and synaptic genes in a spatial and temporal manner in aged and APP/PS1 mice - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38642789/#:~:text=Class%201%20histone%20deacetylases%20differentially,synaptic%20genes%20in%20a%20spatial')
32. AnnotationURLCitation(end_index=13013, start_index=12824, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=development%2C%20generating%20different%20subsets,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
33. AnnotationURLCitation(end_index=13398, start_index=13215, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=deacetylation%20on%20DCs%20by%20genetically,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
34. AnnotationURLCitation(end_index=13684, start_index=13548, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=these%20processes%20is%20unclear,pDC%20and%20mature%20pDC')
35. AnnotationURLCitation(end_index=14082, start_index=13899, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=deacetylation%20on%20DCs%20by%20genetically,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
36. AnnotationURLCitation(end_index=14283, start_index=14156, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=not%20critical%20for%20DC%20development%2C,Multi')
37. AnnotationURLCitation(end_index=14729, start_index=14540, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=development%2C%20generating%20different%20subsets,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
38. AnnotationURLCitation(end_index=15113, start_index=14982, title='Cell cycle-dependent recruitment of HDAC-1 correlates with deacetylation of histone H4 on an Rb–E2F target promoter - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1084028/#:~:text=histone%20H4%20on%20an%20Rb%E2%80%93E2F,1%20can')
39. AnnotationURLCitation(end_index=15380, start_index=15301, title='E2F mediates cell cycle-dependent transcriptional repression in vivo by recruitment of an HDAC1/mSin3B corepressor complex - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/11959842/#:~:text=')
40. AnnotationURLCitation(end_index=15512, start_index=15381, title='Cell cycle-dependent recruitment of HDAC-1 correlates with deacetylation of histone H4 on an Rb–E2F target promoter - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC1084028/#:~:text=histone%20H4%20on%20an%20Rb%E2%80%93E2F,1%20can')
41. AnnotationURLCitation(end_index=16098, start_index=15973, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=individually,an%20increase%20in%20global%20DNA')
42. AnnotationURLCitation(end_index=16226, start_index=16099, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=HDAC1%2F2,are%20core%20components%20of%20several')
43. AnnotationURLCitation(end_index=16756, start_index=16561, title='A comprehensive review of histone deacetylases: implicati...', type='url_citation', url='https://www.degruyterbrill.com/document/doi/10.1515/oncologie-2025-0419/html#:~:text=that%20HDACs%20orchestrate%20crucial%20oncogenic,The%20aberrant%20expression%20and')
44. AnnotationURLCitation(end_index=17250, start_index=17111, title='DNMT1 forms a complex with Rb, E2F1 and HDAC1 and represses transcription from E2F-responsive promoters | Nature Genetics', type='url_citation', url='https://www.nature.com/articles/ng0700_338#:~:text=DNMT1%20forms%20a%20complex%20with,with%20Rb%2C%20E2F1%20and%20HDAC1')
45. AnnotationURLCitation(end_index=17598, start_index=17465, title='The NuRD complex cooperates with DNMTs to maintain silencing of key colorectal tumor suppressor genes - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/23708667/#:~:text=colorectal%20tumor%20suppressor%20genes%20,CONT1%20and')
46. AnnotationURLCitation(end_index=18427, start_index=18300, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=were%20mutated,%CE%BAB%20directly%20but%20can')
47. AnnotationURLCitation(end_index=18582, start_index=18428, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=match%20at%20L87%20association%20of,of%20expression%20of%20these%20genes')
48. AnnotationURLCitation(end_index=18924, start_index=18797, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=were%20mutated,%CE%BAB%20directly%20but%20can')
49. AnnotationURLCitation(end_index=19070, start_index=18925, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=dependent%20reporter%20gene,an%20increased%20basal%20level%20of')
50. AnnotationURLCitation(end_index=19341, start_index=19214, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=%2814%29,interact%20with%20the%20MyoD%20basic')
51. AnnotationURLCitation(end_index=19817, start_index=19729, title='MDM2-HDAC1-mediated deacetylation of p53 is required for its degradation - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/12426395/#:~:text=MDM2,lane')
52. AnnotationURLCitation(end_index=20737, start_index=20571, title='Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/doi/10.1093/nar/gkae1223/7929376#:~:text=In%20conclusion%2C%20these%20results%20show,Providing%20a')
53. AnnotationURLCitation(end_index=21152, start_index=20986, title='Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/doi/10.1093/nar/gkae1223/7929376#:~:text=In%20conclusion%2C%20these%20results%20show,Providing%20a')
54. AnnotationURLCitation(end_index=22246, start_index=22069, title='HDAC1: a promising target for cancer treatment: insights from a thorough analysis of tumor functions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11543092/#:~:text=HDAC1%20exhibited%20high%20expression%20in,migration%20were%20significantly%20inhibited%20by')
55. AnnotationURLCitation(end_index=22633, start_index=22503, title='HDAC1: a promising target for cancer treatment: insights from a thorough analysis of tumor functions - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/39525004/#:~:text=,numerous%20tumors%2C%20and%20strong%20correlations')
56. AnnotationURLCitation(end_index=22829, start_index=22634, title='A comprehensive review of histone deacetylases: implicati...', type='url_citation', url='https://www.degruyterbrill.com/document/doi/10.1515/oncologie-2025-0419/html#:~:text=that%20HDACs%20orchestrate%20crucial%20oncogenic,The%20aberrant%20expression%20and')
57. AnnotationURLCitation(end_index=23449, start_index=23254, title='A comprehensive review of histone deacetylases: implicati...', type='url_citation', url='https://www.degruyterbrill.com/document/doi/10.1515/oncologie-2025-0419/html#:~:text=that%20HDACs%20orchestrate%20crucial%20oncogenic,The%20aberrant%20expression%20and')
58. AnnotationURLCitation(end_index=24219, start_index=24119, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=IV.,have%20been')
59. AnnotationURLCitation(end_index=24679, start_index=24515, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=This%20class%20showed%20inhibition%20of,hence%20panobinostat%20is%20no%20longer')
60. AnnotationURLCitation(end_index=24820, start_index=24680, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=was%20vorinostat%20or%20suberoylanilide%20hydroxamic,23')
61. AnnotationURLCitation(end_index=25024, start_index=24898, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=approved%20for%20multiple%20myeloma%20,42')
62. AnnotationURLCitation(end_index=25462, start_index=25287, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=from%20clinical%20trials%20showed%20that,effective%20against%20lymphomas%20and%20leukemias')
63. AnnotationURLCitation(end_index=25935, start_index=25770, title='HDAC Screening Identifies the HDAC Class I Inhibitor Romidepsin as a Promising Epigenetic Drug for Biliary Tract Cancer - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC8345689/#:~:text=study%2C%20we%20demonstrate%20that%20histone,able%20to%20demonstrate%20that%20BTC')
64. AnnotationURLCitation(end_index=26438, start_index=26327, title='Class I histone deacetylases inhibition reverses memory impairment induced by acute stress in mice - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38635564/#:~:text=by%20acute%20stress%20in%20mice,')
65. AnnotationURLCitation(end_index=26605, start_index=26439, title='Class 1 histone deacetylases differentially modulate memory and synaptic genes in a spatial and temporal manner in aged and APP/PS1 mice - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38642789/#:~:text=Class%201%20histone%20deacetylases%20differentially,synaptic%20genes%20in%20a%20spatial')
66. AnnotationURLCitation(end_index=27056, start_index=26858, title='Rapid degradation of histone deacetylase 1 (HDAC1) reveals essential roles in both gene repression and active transcription | Nucleic Acids Research | Oxford Academic', type='url_citation', url='https://academic.oup.com/nar/article-abstract/doi/10.1093/nar/gkae1223/7929376#:~:text=In%20conclusion%2C%20our%20results%20have,early%20consequences%20of%20HDAC1%20degradation')
67. AnnotationURLCitation(end_index=27511, start_index=27341, title='HDAC1/2 Inhibitor Romidepsin Suppresses DEN-Induced Hepatocellular Carcinogenesis in Mice - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC7304783/#:~:text=HDAC1%2F2%20Inhibitor%20Romidepsin%20Suppresses%20DEN,The%20same%20mouse%20model%20was')
68. AnnotationURLCitation(end_index=27852, start_index=27707, title='Medicinal chemistry advances in targeting class I histone deacetylases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10497394/#:~:text=match%20at%20L112%20Class%20I,an%20emphasis%20on%20class%20I')
69. AnnotationURLCitation(end_index=28005, start_index=27853, title='Medicinal chemistry advances in targeting class I histone deacetylases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10497394/#:~:text=Class%20I%20HDACs%20are%20attractive,an%20emphasis%20on%20class%20I')
70. AnnotationURLCitation(end_index=28249, start_index=28097, title='Medicinal chemistry advances in targeting class I histone deacetylases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10497394/#:~:text=With%20regards%20to%20class%20I,which%20are%20class%20I%20selective')
71. AnnotationURLCitation(end_index=29014, start_index=28865, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=HDAC1%20and%20HDAC2%20are%20class,and%20HDAC2%20can%20regulate%20NF')
72. AnnotationURLCitation(end_index=29173, start_index=29015, title='Mutations on the surface of HDAC1 reveal molecular determinants of specific complex assembly and their requirement for gene regulation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12448893/#:~:text=Histone%20deacetylase%201%20and%202,showed%20that%20retention%20of%20SIN3')
73. AnnotationURLCitation(end_index=29382, start_index=29261, title='ENZYME - 3.5.1.98 histone deacetylase', type='url_citation', url='https://enzyme.expasy.org/EC/3.5.1.98#:~:text=,sequence%20similarity%20and%20domain%20organization')
74. AnnotationURLCitation(end_index=30010, start_index=29838, title='HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/#:~:text=believed%20to%20be%20catalyzed%20by,elevation%20of%20promoter%20histone%20succinylation')
75. AnnotationURLCitation(end_index=30191, start_index=30011, title='HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/#:~:text=desuccinylase%20activity%20in%20vitro,histone%20desuccinylases%20particularly%20important%20for')
76. AnnotationURLCitation(end_index=30638, start_index=30470, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=role%20of%20histone%20modifications%20in,gene%20expression%20changes%2C%20a%20substantial')
77. AnnotationURLCitation(end_index=30766, start_index=30639, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=HDAC1%2F2,are%20core%20components%20of%20several')
78. AnnotationURLCitation(end_index=31068, start_index=30880, title='HDAC1 and HDAC2 orchestrate Wnt signaling to regulate neural progenitor transition during brain development - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11367519/#:~:text=neural%20differentiation%2C%20yet%20the%20governing,rescued%20the%20disrupted%20cortical%20architecture')
79. AnnotationURLCitation(end_index=31298, start_index=31115, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=deacetylation%20on%20DCs%20by%20genetically,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
80. AnnotationURLCitation(end_index=32749, start_index=32577, title='HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/#:~:text=believed%20to%20be%20catalyzed%20by,elevation%20of%20promoter%20histone%20succinylation')
81. AnnotationURLCitation(end_index=33276, start_index=33128, title='Medicinal chemistry advances in targeting class I histone deacetylases - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10497394/#:~:text=Histone%20deacetylases%20,via%20histone%20acetyl%20transferases')
82. AnnotationURLCitation(end_index=33424, start_index=33303, title='ENZYME - 3.5.1.98 histone deacetylase', type='url_citation', url='https://enzyme.expasy.org/EC/3.5.1.98#:~:text=,sequence%20similarity%20and%20domain%20organization')
83. AnnotationURLCitation(end_index=33558, start_index=33425, title='ENZYME - 3.5.1.98 histone deacetylase', type='url_citation', url='https://enzyme.expasy.org/EC/3.5.1.98#:~:text=Reaction%20catalysed%20,histone%5D%20%2B%20acetate%20Comment%28s')
84. AnnotationURLCitation(end_index=33786, start_index=33637, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=HDAC1%20and%20HDAC2%20are%20class,and%20HDAC2%20can%20regulate%20NF')
85. AnnotationURLCitation(end_index=33993, start_index=33835, title='Mutations on the surface of HDAC1 reveal molecular determinants of specific complex assembly and their requirement for gene regulation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12448893/#:~:text=Histone%20deacetylase%201%20and%202,showed%20that%20retention%20of%20SIN3')
86. AnnotationURLCitation(end_index=34264, start_index=34108, title='Hdac1 histone deacetylase 1 [Mus musculus (house mouse)] - Gene - NCBI', type='url_citation', url='https://www.ncbi.nlm.nih.gov/gene/433759#:~:text=Enables%20several%20functions%2C%20including%20E,Orthologous%20to%20human%20HDAC1')
87. AnnotationURLCitation(end_index=34486, start_index=34298, title='HDAC1 and HDAC2 orchestrate Wnt signaling to regulate neural progenitor transition during brain development - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11367519/#:~:text=neural%20differentiation%2C%20yet%20the%20governing,rescued%20the%20disrupted%20cortical%20architecture')
88. AnnotationURLCitation(end_index=34746, start_index=34557, title='The histone deacetylase HDAC1 controls dendritic cell development and anti-tumor immunity - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/38829740/#:~:text=development%2C%20generating%20different%20subsets,HDAC1%20controls%20expression%2C%20chromatin%20accessibility')
89. AnnotationURLCitation(end_index=34960, start_index=34833, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=were%20mutated,%CE%BAB%20directly%20but%20can')
90. AnnotationURLCitation(end_index=35088, start_index=34961, title='The p65 (RelA) Subunit of NF-κB Interacts with the Histone Deacetylase (HDAC) Corepressors HDAC1 and HDAC2 To Negatively Regulate Gene Expression - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC99882/#:~:text=%2814%29,interact%20with%20the%20MyoD%20basic')
91. AnnotationURLCitation(end_index=35423, start_index=35290, title='The NuRD complex cooperates with DNMTs to maintain silencing of key colorectal tumor suppressor genes - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/23708667/#:~:text=colorectal%20tumor%20suppressor%20genes%20,CONT1%20and')
92. AnnotationURLCitation(end_index=35662, start_index=35490, title='HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/#:~:text=believed%20to%20be%20catalyzed%20by,elevation%20of%20promoter%20histone%20succinylation')
93. AnnotationURLCitation(end_index=35843, start_index=35663, title='HDAC1/2/3 are major histone desuccinylases critical for promoter desuccinylation - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC10425439/#:~:text=desuccinylase%20activity%20in%20vitro,histone%20desuccinylases%20particularly%20important%20for')
94. AnnotationURLCitation(end_index=36087, start_index=35919, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=role%20of%20histone%20modifications%20in,gene%20expression%20changes%2C%20a%20substantial')
95. AnnotationURLCitation(end_index=36215, start_index=36088, title='Essential roles of HDAC1 and 2 in lineage development and genome-wide DNA methylation during mouse preimplantation development - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/31533525/#:~:text=HDAC1%2F2,are%20core%20components%20of%20several')
96. AnnotationURLCitation(end_index=36419, start_index=36285, title='A single allele of Hdac2 but not Hdac1 is sufficient for normal mouse brain development in the absence of its paralog - PubMed', type='url_citation', url='https://pubmed.ncbi.nlm.nih.gov/24449838/#:~:text=HDAC1%20and%20HDAC2%2C%20we%20expressed,brains%20showed')
97. AnnotationURLCitation(end_index=36676, start_index=36499, title='HDAC1: a promising target for cancer treatment: insights from a thorough analysis of tumor functions - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC11543092/#:~:text=HDAC1%20exhibited%20high%20expression%20in,migration%20were%20significantly%20inhibited%20by')
98. AnnotationURLCitation(end_index=36908, start_index=36713, title='A comprehensive review of histone deacetylases: implicati...', type='url_citation', url='https://www.degruyterbrill.com/document/doi/10.1515/oncologie-2025-0419/html#:~:text=that%20HDACs%20orchestrate%20crucial%20oncogenic,The%20aberrant%20expression%20and')
99. AnnotationURLCitation(end_index=37040, start_index=36940, title='HDAC inhibitors as anticancer drugs: chemical diversity, clinical trials, challenges and perspectives - PMC', type='url_citation', url='https://pmc.ncbi.nlm.nih.gov/articles/PMC12805814/#:~:text=IV.,have%20been')