SPT16 is a core subunit of the FACT complex (Facilitates Chromatin Transcription), an essential histone chaperone that reorganizes nucleosomes during transcription, DNA replication, and DNA repair. SPT16 comprises three domains (N-terminal, middle with double PH domains, and C-terminal acidic region) that enable interaction with histones H3/H4 and H2A/H2B dimers, facilitating nucleosome disassembly during polymerase passage and nucleosome reassembly afterward. SPT16 is also known as CDC68 (cell division control protein 68).
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0006337 nucleosome disassembly | IBA GO_REF:0000033 | ACCEPT | Summary: Nucleosome disassembly is a well-established core function of SPT16/FACT during transcription elongation. IBA (ortholog inference) is appropriate evidence for this deeply characterized function. Reason: SPT16 is a core component of FACT complex that actively facilitates nucleosome disassembly ahead of RNA polymerase II during transcription. The deep research and extensive literature (including Perplexity review citing structural studies showing Spt16 interactions with H3-H4 and H2A-H2B during nucleosome disruption) strongly support this annotation. This is a primary and essential function. Propagation Review Root cause: SOURCE STALE OR MISSING Sources checked: PANTHER:PTN000360139 Β· Spt16 FACT histone chaperone ancestral node in PTHR13980 SOURCE STALE OR MISSING GOA traces this 2025 IBA to PTN000360139, and that ancestral node still exists in the local PTHR13980 PAINT export, but current PAINT no longer carries the exact GO:0006337 term there; the node now carries the sibling GO:0140673 transcription elongation-coupled chromatin remodeling process under chromatin remodeling. Supporting Evidence: file:yeast/SPT16/SPT16-deep-research-perplexity.md See deep research file for comprehensive analysis file:yeast/SPT16/SPT16-deep-research-falcon.md - helps manage nucleosome dynamics (both **disassembly** and **reassembly**) as RNAPII traverses genes, (byrd2024assessingcontributionsof pages 1-2) |
| GO:0032784 regulation of DNA-templated transcription elongation | IBA GO_REF:0000033 | MODIFY | Summary: SPT16/FACT directly performs elongation-coupled chromatin remodeling rather than merely regulating transcription elongation from outside the chromatin-transaction machinery. Reason: The old IBA term GO:0032784 is a regulation-of-transcription-elongation term. SPT16/FACT is better described by GO:0140673 transcription elongation-coupled chromatin remodeling because FACT travels with elongating RNA polymerase II and reorganizes nucleosomes as a direct part of polymerase transit through chromatin. Current PTHR13980 PAINT has made the same re-term on PTN000360139, placing GO:0140673 on the ancestor instead of GO:0032784. Propagation Review Root cause: TERM SCOPING PROBLEM Sources checked: PANTHER:PTN000360139 Β· Spt16 FACT histone chaperone ancestral node in PTHR13980 SUPPORTS TRANSFER GOA traces this 2025 IBA to PTN000360139. That ancestor still exists in the local PTHR13980 PAINT export and now carries GO:0140673 transcription elongation-coupled chromatin remodeling, which captures direct FACT-coupled remodeling instead of the old regulation branch. Proposed replacements: transcription elongation-coupled chromatin remodeling Supporting Evidence: file:yeast/SPT16/SPT16-deep-research-falcon.md - is required for efficient RNAPII transcription on chromatin templates and functions as a **nucleosome-templated elongation factor**, (schweighofer2025biochemicalinsightsinto pages 22-25, hou2025characterizingthefunctional pages 20-23) PMID:40405832 Spt16's IDR regulates chromatin reassembly at the coding sequence in the wake of elongating RNA polymerase II. |
| GO:0035101 FACT complex | IBA GO_REF:0000033 | ACCEPT | Summary: SPT16 is a core structural component of the FACT complex. This annotation represents membership in the complex with strong phylogenetic support. Reason: SPT16 forms an obligate heterodimeric complex with POB3 (Pob3p) as documented in UniProt and extensively in the literature. The current PTHR13980 PAINT export places FACT-complex membership on the Spt16 ancestral node PTN000360139, matching this conserved structural annotation. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000360139 Β· Spt16 FACT histone chaperone ancestral node in PTHR13980 SUPPORTS TRANSFER Current PAINT carries GO:0035101 on PTN000360139 with experimentally annotated Spt16 descendants from budding yeast, pombe, animals and plants, so the node supports conserved FACT complex membership for this S. cerevisiae target. Supporting Evidence: file:yeast/SPT16/SPT16-deep-research-falcon.md Spt16 is the large, essential subunit of the conserved yeast FACT histone chaperone complex; in *S. cerevisiae* it forms a heterodimer with Pob3, and budding-yeast FACT function additionally depends on the HMGB protein Nhp6 for efficient nucleosome engagement. |
| GO:0005634 nucleus | IEA GO_REF:0000044 | ACCEPT | Summary: SPT16 is localized to the nucleus, where it functions in chromatin-associated processes. Reason: Nuclear localization is well-established for SPT16 through multiple studies showing chromatin-association and co-localization with active transcription sites. While IEA is less specific than experimental evidence, nuclear localization is a foundational fact confirmed by direct observation (PMID:10413469). This is a valid cellular component annotation. Supporting Evidence: file:yeast/SPT16/SPT16-deep-research-falcon.md The evidence supports that Spt16 is **nuclear and chromatin-associated**, acting at: |
| GO:0005694 chromosome | IEA GO_REF:0000044 | ACCEPT | Summary: SPT16 is localized to chromatin/chromosomes where it functions in nucleosome reorganization during transcription and replication. Reason: SPT16 specifically associates with chromatin and DNA during its biological functions. This is explicitly documented - UniProt states 'Colocalizes with RNA polymerase II on chromatin' and associates with coding regions of histone genes. The annotation is accurate and important for describing where the protein functions. |
| GO:0006260 DNA replication | IEA GO_REF:0000043 | ACCEPT | Summary: SPT16 is involved in DNA replication through its role in nucleosome disassembly ahead of replication forks and histone recycling to daughter strands. Reason: SPT16/FACT is essential for normal replication fork progression. The deep research documents that FACT associates with replication fork components (MCM2-7, Pol alpha) and that SSRP1/SPT16 depletion slows replication forks. The Spt16-N domain interacts with MCM2-7 complex and fork protection complex, enabling parental histone recycling during replication. Supporting Evidence: file:yeast/SPT16/SPT16-deep-research-falcon.md - The Spt16 N-terminal domain binds **Tof1** (fork protection complex) and **MCM2-7** helicase in yeast, linking FACT to fork-associated chromatin transactions. (schweighofer2025biochemicalinsightsintoa pages 22-25, dolson2024impactofthe pages 16-19) - FACT is reported to physically interact with **DNA polymerase Ξ±** in yeast. |
| GO:0006281 DNA repair | IEA GO_REF:0000043 | ACCEPT | Summary: SPT16 participates in DNA repair, particularly base excision repair, through cooperation with chromatin remodelers. Reason: UniProt function section states FACT plays a role in DNA repair. The deep research documentation mentions FACT recruitment to DNA damage sites and cooperation with remodelers to expose damaged DNA for repair (BER pathway). While less extensively characterized than transcription roles, the involvement is documented and scientifically valid. |
| GO:0006351 DNA-templated transcription | IEA GO_REF:0000043 | ACCEPT | Summary: SPT16 is fundamentally involved in DNA-templated transcription through its role in nucleosome dynamics during transcription. Reason: SPT16/FACT is a transcription elongation factor essential for efficient transcription through chromatin. This broad annotation captures the core transcriptional role of the protein. IEA from UniProt keyword mapping is appropriate for this well-established function. |
| GO:0006974 DNA damage response | IEA GO_REF:0000043 | ACCEPT | Summary: SPT16 participates in DNA damage response through recruitment to damaged chromatin and cooperation with repair machinery. Reason: UniProt function section mentions DNA repair role and the deep research documents FACT recruitment to DNA damage sites. The involvement in BER and interaction with DNA damage-responsive proteins supports this annotation. |
| GO:0010468 regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: While SPT16 does participate in gene expression regulation, this term is very broad and less informative than the specific transcription annotations already present. Reason: This annotation is not incorrect, but it represents a general consequence of SPT16's core transcriptional functions rather than a distinct molecular function. More specific GO terms (transcription elongation, nucleosome disassembly, etc.) better capture SPT16's specific contributions to gene regulation. The annotation should be retained because it is accurate, but marked as non-core. |
| GO:0034728 nucleosome organization | IEA GO_REF:0000117 | ACCEPT | Summary: Nucleosome organization is a core function of SPT16/FACT, encompassing both disassembly and reassembly activities during transcription and replication. Reason: SPT16 directly organizes nucleosomes by controlling their disassembly and reassembly. This is documented throughout literature and is one of the defining functions of the protein. The term appropriately captures the holistic role of nucleosome management. |
| GO:0035101 FACT complex | IEA GO_REF:0000120 | ACCEPT | Summary: This duplicate annotation (same GO term as IBA annotation above) documents FACT complex membership through automated methods. Both evidence codes are valid. Reason: Duplicate annotations with different evidence codes are acceptable in GO. The IEA source (InterPro) provides orthogonal confirmation of FACT complex membership. Both IBA and IEA annotations should be retained. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: SPT16 engages in multiple specific protein-protein interactions documented through mass spectrometry and other methods. However, 'protein binding' is a generic term that doesn't specify the functional nature of these interactions. Reason: This systematic mass-spectrometry row may document a real physical association, but the generic GO:0005515 protein binding term is too broad to describe SPT16/FACT molecular function. More specific histone and nucleosome binding activities are already captured by separate direct annotations, and this generic row should be removed rather than retained as non-core. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:11805837 Systematic identification of protein complexes in Saccharomy... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:11805837 Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. |
| GO:0005515 protein binding | IPI PMID:11927560 The Paf1 complex physically and functionally associates with... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:11927560 The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. |
| GO:0005515 protein binding | IPI PMID:11927560 The Paf1 complex physically and functionally associates with... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:11927560 The Paf1 complex physically and functionally associates with transcription elongation factors in vivo. |
| GO:0005515 protein binding | IPI PMID:12077334 Yng1p modulates the activity of Sas3p as a component of the ... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12077334 Yng1p modulates the activity of Sas3p as a component of the yeast NuA3 Hhistone acetyltransferase complex. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevi... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:12242279 RNA polymerase II elongation factors of Saccharomyces cerevisiae: a targeted proteomics approach. |
| GO:0005515 protein binding | IPI PMID:14759368 High-definition macromolecular composition of yeast RNA-proc... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:14759368 High-definition macromolecular composition of yeast RNA-processing complexes. |
| GO:0005515 protein binding | IPI PMID:14759368 High-definition macromolecular composition of yeast RNA-proc... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:14759368 High-definition macromolecular composition of yeast RNA-processing complexes. |
| GO:0005515 protein binding | IPI PMID:16299494 A phosphatase complex that dephosphorylates gammaH2AX regula... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:16299494 A phosphatase complex that dephosphorylates gammaH2AX regulates DNA damage checkpoint recovery. |
| GO:0005515 protein binding | IPI PMID:16429126 Proteome survey reveals modularity of the yeast cell machine... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:16429126 Proteome survey reveals modularity of the yeast cell machinery. |
| GO:0005515 protein binding | IPI PMID:16554755 Global landscape of protein complexes in the yeast Saccharom... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:16554755 Global landscape of protein complexes in the yeast Saccharomyces cerevisiae. |
| GO:0005515 protein binding | IPI PMID:20489023 A global protein kinase and phosphatase interaction network ... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:20489023 A global protein kinase and phosphatase interaction network in yeast. |
| GO:0005515 protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome. |
| GO:0005515 protein binding | IPI PMID:31582854 FACT mediates cohesin function on chromatin. | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:31582854 FACT mediates cohesin function on chromatin. |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: Multiple instances of the same GO:0005515 term with different specific interaction partners from IntAct database. Reason: Each IPI row may document a real physical association, but GO:0005515 protein binding is too generic to describe SPT16/FACT molecular function. These IntAct-derived entries should be removed rather than retained as non-core unless their cited papers justify a more specific molecular function term. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome. |
| GO:0042802 identical protein binding | IPI PMID:14759368 High-definition macromolecular composition of yeast RNA-proc... | REMOVE | Summary: SPT16 forms homodimeric interactions documented through mass spectrometry (PMID:14759368). However, SPT16 primarily functions as a heterodimer with POB3 in the FACT complex. Reason: The high-throughput interaction may record a real physical association, but this row does not provide positive support for a physiologic Spt16 homodimer. The established functional form is the Spt16-Pob3 FACT heterodimer, so this generic self-binding assertion should be removed like the GO:0005515 rows from the same interactome sources. Supporting Evidence: PMID:14759368 High-definition macromolecular composition of yeast RNA-processing complexes. |
| GO:0042802 identical protein binding | IPI PMID:21179020 Defining the budding yeast chromatin-associated interactome. | REMOVE | Summary: SPT16 forms homodimeric interactions documented through chromatin-associated interactome studies (PMID:21179020). However, SPT16 primarily functions as a heterodimer with POB3. Reason: The chromatin-associated interactome row may record a real physical association, but it does not provide positive support for a physiologic Spt16 homodimer. The established functional form is the Spt16-Pob3 FACT heterodimer, so this generic self-binding assertion should be removed like the GO:0005515 rows from the same interactome sources. Supporting Evidence: PMID:21179020 Defining the budding yeast chromatin-associated interactome. |
| GO:0006261 DNA-templated DNA replication | NAS PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 t... | ACCEPT | Summary: DNA-templated DNA replication is directly facilitated by SPT16/FACT. NAS (non-traceable author statement) from ComplexPortal reference is appropriate for this well-characterized function. Reason: SPT16/FACT involvement in DNA replication is extensively documented. The protein associates with replication machinery (MCM2-7, Pol alpha), facilitates fork progression, and mediates parental histone recycling to daughter strands. Multiple studies document this function. Supporting Evidence: PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes. |
| GO:0034728 nucleosome organization | NAS PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 t... | ACCEPT | Summary: Nucleosome organization during DNA replication is a key SPT16 function, complementary to its transcriptional roles. Reason: This represents nucleosome management during replication, distinct from (though overlapping with) transcriptional nucleosome organization. Both processes are central to FACT function and well-documented in the literature. Supporting Evidence: PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes. |
| GO:1902275 regulation of chromatin organization | NAS PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 t... | ACCEPT | Summary: SPT16/FACT actively regulates chromatin organization by controlling nucleosome structure and positioning throughout the genome. Reason: This term appropriately captures FACT's regulatory role in chromatin dynamics. The protein doesn't merely disassemble and reassemble nucleosomes passively but actively orchestrates their organization in response to biological requirements. This is distinct from and more accurate than the more passive 'nucleosome organization' term. Supporting Evidence: PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes. |
| GO:0006325 chromatin organization | IDA PMID:19683499 yFACT induces global accessibility of nucleosomal DNA withou... | ACCEPT | Summary: Chromatin organization is a primary direct activity of SPT16 demonstrated through direct biochemical and cell biological assays. Reason: IDA evidence from direct assays (PMID:19683499) documents SPT16's role in chromatin organization. The protein's ability to facilitate nucleosomal DNA accessibility and reorganize chromatin structure is directly demonstrated. This is core function. Supporting Evidence: PMID:19683499 yFACT induces global accessibility of nucleosomal DNA without H2A-H2B displacement. |
| GO:0000785 chromatin | IDA PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential... | ACCEPT | Summary: SPT16 localizes to chromatin and is a structural component of chromatin-associated FACT complexes. Reason: Direct evidence from PMID:10413469 documents that SPT16 is chromatin-associated, nuclear, and copurifies with chromatin. This is a valid cellular component annotation with strong experimental support. Supporting Evidence: PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential, abundant heterodimer that is nuclear, chromatin-associated, and copurifies with DNA polymerase alpha. |
| GO:0007063 regulation of sister chromatid cohesion | IDA PMID:31582854 FACT mediates cohesin function on chromatin. | KEEP AS NON CORE | Summary: SPT16/FACT regulates sister chromatid cohesion through cooperation with cohesin complex on chromatin. Reason: PMID:31582854 provides direct experimental evidence that FACT mediates cohesin function on chromatin. This annotation represents a documented but more specialized function of SPT16 beyond its primary transcription/replication roles. The annotation is scientifically valid. Supporting Evidence: PMID:31582854 Cohesin is a regulator of genome architecture with roles in sister chromatid cohesion and chromosome compaction. |
| GO:0035101 FACT complex | IGI PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucl... | ACCEPT | Summary: SPT16 is part of the FACT complex, demonstrated through genetic interaction studies where loss of SPT16 affects nucleosome-binding complex assembly. Reason: IGI evidence (genetic interaction with NHP6 - PMID:11432837) documents FACT complex assembly. SPT16 cooperates with NHP6 proteins to form the nucleosome-binding SPN complex. This genetic evidence properly supports the complex assembly annotation. Supporting Evidence: PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. |
| GO:0035101 FACT complex | IPI PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucl... | ACCEPT | Summary: SPT16 physically interacts with POB3 (with column SGD:S000004534) to form the FACT heterodimer, directly demonstrated. Reason: IPI evidence documents the obligate SPT16-POB3 interaction that forms the core of the FACT complex. This is well-established biochemically and is an essential part of SPT16 function. Supporting Evidence: PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. |
| GO:0005515 protein binding | IPI PMID:27226635 The Modifier of Transcription 1 (Mot1) ATPase and Spt16 Hist... | REMOVE | Summary: SPT16 interacts with Mot1 ATPase as documented in the context of transcriptional regulation through preinitiation complex assembly. Reason: The Mot1 interaction is experimentally reported, but GO:0005515 protein binding is too generic to capture the functional relationship between Mot1 and FACT during preinitiation-complex assembly and nucleosome organization. Remove the uninformative generic MF unless the evidence can support a more specific activity term. Supporting Evidence: PMID:27226635 The Modifier of Transcription 1 (Mot1) ATPase and Spt16 Histone Chaperone Co-regulate Transcription through Preinitiation Complex Assembly and Nucleosome Organization. |
| GO:0003682 chromatin binding | IDA PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential... | ACCEPT | Summary: Chromatin binding is a direct biochemical activity of SPT16, demonstrated through binding assays. Reason: IDA evidence from PMID:10413469 directly shows SPT16 binds to chromatin. This molecular function annotation is supported by direct experimental evidence. The 'contributes_to' relationship indicates this is one of multiple activities rather than the sole function. Supporting Evidence: PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential, abundant heterodimer that is nuclear, chromatin-associated, and copurifies with DNA polymerase alpha. |
| GO:0006261 DNA-templated DNA replication | IPI PMID:9199353 The Saccharomyces cerevisiae DNA polymerase alpha catalytic ... | ACCEPT | Summary: SPT16 participates in DNA replication through physical interaction with DNA polymerase alpha, directly demonstrated. Reason: IPI evidence from PMID:9199353 documents SPT16's interaction with Pol1 (DNA polymerase alpha) catalytic subunit, establishing a direct physical link to replication machinery. This supports SPT16's functional involvement in replication processes. Supporting Evidence: PMID:9199353 The Saccharomyces cerevisiae DNA polymerase alpha catalytic subunit interacts with Cdc68/Spt16 and with Pob3, a protein similar to an HMG1-like protein. file:yeast/SPT16/SPT16-deep-research-falcon.md - FACT is reported to physically interact with **DNA polymerase Ξ±** in yeast. |
| GO:0006334 nucleosome assembly | IDA PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 t... | ACCEPT | Summary: Nucleosome assembly is a core molecular function of SPT16/FACT, demonstrated through direct biochemical assays showing nucleosome deposition activity. Reason: IDA evidence from PMID:12952948 documents SPT16's role in nucleosome assembly. The protein actively facilitates reassembly of nucleosomes following polymerase passage and during DNA replication. This is a primary and essential function. Supporting Evidence: PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 to form yFACT complexes and to reorganize nucleosomes. |
| GO:0006334 nucleosome assembly | IDA PMID:15082784 Structural features of nucleosomes reorganized by yeast FACT... | ACCEPT | Summary: Nucleosome assembly is a core molecular function of SPT16/FACT, demonstrated through structural studies of FACT-reorganized nucleosomes. Reason: IDA evidence from PMID:15082784 documents structural features of nucleosomes reorganized by FACT, demonstrating SPT16's role in nucleosome assembly. Multiple evidence sources strengthen this annotation. Supporting Evidence: PMID:15082784 Structural features of nucleosomes reorganized by yeast FACT and its HMG box component, Nhp6. |
| GO:0031491 nucleosome binding | IDA PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucl... | ACCEPT | Summary: Nucleosome binding is a core molecular function of SPT16, directly demonstrated through biochemical assays. Reason: IDA evidence from PMID:11432837 directly documents SPT16 nucleosome binding. The protein's multiple histone-binding domains enable this core activity. The 'contributes_to' relationship appropriately reflects that this is part of the multi-domain histone chaperone activity. Supporting Evidence: PMID:11432837 Spt16-Pob3 and the HMG protein Nhp6 combine to form the nucleosome-binding factor SPN. |
| GO:0042393 histone binding | IDA PMID:18089575 Structural and functional analysis of the Spt16p N-terminal ... | ACCEPT | Summary: Histone binding is a core molecular function of SPT16, with direct biochemical evidence of interactions with histone H3, H4, H2A, and H2B. Reason: IDA evidence from PMID:18089575 directly documents histone binding. The N-terminal domain binds H3-H4, middle domain binds H3-H4 tetramers, and C-terminal domain binds H2A-H2B dimers. These interactions are structural and mechanistically essential for nucleosome chaperone function. Supporting Evidence: PMID:18089575 Structural and functional analysis of the Spt16p N-terminal domain reveals overlapping roles of yFACT subunits. file:yeast/SPT16/SPT16-deep-research-falcon.md - a **middle domain** that contacts **(H3βH4)β**, file:yeast/SPT16/SPT16-deep-research-falcon.md FACT/Spt16 is described as atypical because it engages both major histone modules, enabling coordinated nucleosome disassembly/reassembly: |
| GO:0045899 positive regulation of RNA polymerase II transcription preinitiation complex assembly | IDA PMID:15987999 The yeast FACT complex has a role in transcriptional initiat... | ACCEPT | Summary: SPT16/FACT has a direct role in preinitiation complex assembly and transcription initiation through FACT-mediated nucleosome disassembly at promoters. Reason: IDA evidence from PMID:15987999 directly demonstrates FACT's role in transcription initiation. The protein facilitates PIC assembly by clearing nucleosomal barriers at promoters and promoting TBP binding to TATA boxes. This is distinct from and complementary to elongation functions. Supporting Evidence: PMID:15987999 The yeast FACT complex has a role in transcriptional initiation. file:yeast/SPT16/SPT16-deep-research-falcon.md In yeast, Spt16/FACT is a nucleosome-templated transcription factor that promotes productive RNAPII elongation, supports nucleosome disassembly and reassembly during polymerase passage, suppresses cryptic initiation, and contributes to promoter function/PIC formation. PMID:40405832 disassembly by Spt16's IDR stimulates the pre-initiation complex (PIC) formation at the promoter, and hence transcription initiation. |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IGI PMID:15987999 The yeast FACT complex has a role in transcriptional initiat... | ACCEPT | Summary: SPT16 positively regulates transcription initiation by RNA polymerase II through genetic interaction with initiation factors. Reason: IGI evidence from PMID:15987999 documents functional interaction between SPT16 and transcription initiation machinery. The genetic interactions establish SPT16's role in promoting initiation. This complements the direct IDA evidence. Supporting Evidence: PMID:15987999 The yeast FACT complex has a role in transcriptional initiation. |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IMP PMID:19574230 FACT and the proteasome promote promoter chromatin disassemb... | ACCEPT | Summary: SPT16 positively regulates transcription initiation by RNA Pol II, demonstrated through mutation/depletion studies showing defects in initiation when SPT16 is inactivated. Reason: IMP evidence from PMID:19574230 documents that promoter chromatin disassembly and transcriptional initiation require both FACT and proteasome function. Loss of FACT function impairs initiation, supporting this annotation with the strongest type of mechanistic evidence. Supporting Evidence: PMID:19574230 FACT and the proteasome promote promoter chromatin disassembly and transcriptional initiation. |
| GO:0000511 H2A-H2B histone complex chaperone activity | IBA GO_REF:0000033 | ACCEPT | Summary: The PTHR13980 PAINT placement captures Spt16/FACT's conserved contribution to H2A-H2B histone-dimer chaperone activity. Reason: Current PAINT places H2A-H2B histone complex chaperone activity on the conserved Spt16/FACT ancestral node. This is consistent with the 2025 S. cerevisiae Spt16 IDR study showing that Spt16's C-terminal IDR facilitates H2A-H2B eviction at GAL promoters and regulates coding-sequence chromatin reassembly after RNA polymerase II passage. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000360139 Β· Spt16 FACT histone chaperone ancestral node in PTHR13980 SUPPORTS TRANSFER Current PAINT carries GO:0000511 on PTN000360139 from the PomBase spt16 seed, and budding-yeast Spt16 has direct target-species evidence for H2A-H2B eviction. Supporting Evidence: PMID:40405832 Here, we show that Spt16's IDR facilitates the eviction of histone H2A-H2B dimer |
| GO:0005515 protein binding | IPI PMID:37968396 The social and structural architecture of the yeast protein ... | REMOVE | Summary: The current IntAct row records an RNA polymerase II elongation-factor interaction but still uses generic protein binding. Reason: The PMID:37968396 protein interaction row may document a real association between FACT and the elongation factor Spt5, but GO:0005515 protein binding is too generic to describe the Spt16/FACT histone-chaperone mechanism and adds no specific molecular function beyond the retained chromatin-, nucleosome-, histone-, and H2A-H2B-binding rows. Supporting Evidence: PMID:37968396 The social and structural architecture of the yeast protein interactome. |
| GO:0005634 nucleus | EXP PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential... | ACCEPT | Summary: Direct experimental evidence places Spt16 in the nucleus. Reason: The experimental UniProt row is consistent with PMID:10413469, which localized Spt16, Pob3 and Pol1 to the nucleus. Nuclear localization is a core cellular context for Spt16's chromatin and DNA-replication activities. Supporting Evidence: PMID:10413469 Spt16, Pob3, and Pol1 proteins were all found to localize to the nucleus in S. cerevisiae. |
| GO:0005694 chromosome | EXP PMID:10413469 Spt16 and Pob3 of Saccharomyces cerevisiae form an essential... | ACCEPT | Summary: Direct experimental evidence places a fraction of Spt16-Pob3 on chromatin. Reason: Spt16/FACT functions on nucleosomes in chromosome-associated chromatin, and PMID:10413469 directly reports that part of the cellular Spt16-Pob3 pool is chromatin-associated. Supporting Evidence: PMID:10413469 A portion of the total cellular Spt16-Pob3 was found to be chromatin-associated |
| GO:0006335 DNA replication-dependent chromatin assembly | NAS PMID:12952948 Multiple Nhp6 molecules are required to recruit Spt16-Pob3 t... | ACCEPT | Summary: FACT has an established replication-coupled chromatin-assembly role through fork-associated nucleosome disassembly/reassembly and parental histone recycling. Reason: The ComplexPortal NAS row is a biologically sound representation of FACT's role in replication-coupled chromatin assembly. Although PMID:12952948 itself focuses on Nhp6-mediated recruitment of Spt16-Pob3 to reorganized nucleosomes, Spt16-Pob3 also physically couples to DNA polymerase alpha and supports nucleosome management during chromosomal DNA replication. Supporting Evidence: PMID:12952948 We propose that the coordinated action of multiple Nhp6 molecules is required to convert nucleosomes to an alternative form as the first step in a two-step reorganization of nucleosomes with the second step being dependent on Spt16-Pob3. PMID:10413469 Some of the Spt16-Pob3 complex was found to copurify with the yeast DNA polymerase alpha/primase complex, further supporting a connection between Spt16-Pob3 and DNA replication. |
| GO:0006366 transcription by RNA polymerase II | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: ARBA assigns the broad RNA polymerase II transcription process that covers Spt16/FACT's promoter and elongation-coupled chromatin remodeling. Reason: Transcription by RNA polymerase II is broader than the most informative FACT terms, but it is accurate for a histone chaperone that directly promotes Pol II initiation and elongation through chromatin. Supporting Evidence: PMID:15987999 The yeast FACT complex has a role in transcriptional initiation. PMID:40405832 Spt16's IDR regulates chromatin reassembly at the coding sequence in the wake of elongating RNA polymerase II. |
| GO:0035101 FACT complex | IPI PMID:32701054 Antagonistic control of DDK binding to licensed replication ... | ACCEPT | Summary: The ComplexPortal IPI row retains Spt16 as a subunit of the purified Spt16-Pob3 FACT complex. Reason: Spt16-Pob3 is the established budding-yeast FACT heterodimer, and the PMID:32701054 reconstituted-replication study purified FACT from yeast cells co-expressing SPT16 and tagged POB3. Supporting Evidence: PMID:32701054 FACT complex was purified after overexpression in yeast cells harboring codon-optimized copies of SPT16 and N-terminally CBP-tagged POB3 |
| GO:0040029 epigenetic regulation of gene expression | IEA GO_REF:0000117 | KEEP AS NON CORE | Summary: FACT affects epigenetic gene regulation through chromatin maintenance, but this ARBA term is broader than its direct nucleosome-chaperone activities. Reason: Spt16 participates in chromatin-based maintenance of gene-expression states during transcription and DNA replication, so the ARBA term is not false. It should be kept as non-core because the review's chromatin remodeling, histone chaperone, nucleosome binding and FACT-complex rows state the direct mechanism. |
| GO:0045815 transcription initiation-coupled chromatin remodeling | IMP PMID:40405832 An Intrinsically Disordered Region of the FACT Subunit, Spt1... | ACCEPT | Summary: Spt16 promotes promoter chromatin disassembly that stimulates Pol II preinitiation-complex formation. Reason: The 2025 Spt16 IDR study directly connects Spt16-mediated H2A-H2B eviction and promoter chromatin disassembly to stimulation of preinitiation-complex formation in vivo. Supporting Evidence: PMID:40405832 chromatin disassembly by Spt16's IDR stimulates the pre-initiation complex (PIC) formation |
| GO:0060261 positive regulation of transcription initiation by RNA polymerase II | IGI PMID:15987999 The yeast FACT complex has a role in transcriptional initiat... | ACCEPT | Summary: A second genetic-interaction row from PMID:15987999 supports Spt16's positive role in Pol II transcription initiation. Reason: This IGI row differs from the existing accepted PMID:15987999 row only in the interacting transcription-initiation factor recorded by GOA. The paper shows that yFACT promotes TBP binding on chromatin and that spt16 mutations genetically interact with TBP/TFIIA machinery, so the row supports the same promoter function. Supporting Evidence: PMID:15987999 The SPT16 gene encodes a subunit of yFACT, and we show that certain spt16 mutations are synthetically lethal with TBP mutants. |
| GO:0140673 transcription elongation-coupled chromatin remodeling | IBA GO_REF:0000033 | ACCEPT | Summary: Current PAINT now places the direct FACT-shaped transcription elongation-coupled chromatin-remodeling term on the conserved Spt16 ancestral node. Reason: GO:0140673 is the same term this review had proposed as a replacement for the older GO:0032784 IBA, and it captures Spt16/FACT's direct nucleosome reassembly activity in the wake of elongating RNA polymerase II better than a generic regulation-of-elongation parent. The PAINT source is appropriate; PTHR13980 now carries this term on PTN000360139, and the human seed belongs to the orthologous FACT SPT16 subunit. Propagation Review Root cause: NO FAILURE CORE Sources checked: PANTHER:PTN000360139 Β· Spt16 FACT histone chaperone ancestral node in PTHR13980 SUPPORTS TRANSFER Current PAINT carries GO:0140673 on PTN000360139 with human SUPT16H as the seed, matching the conserved FACT-dependent Pol II elongation function in budding-yeast Spt16. Supporting Evidence: PMID:40405832 Spt16's IDR regulates chromatin reassembly at the coding sequence in the wake of elongating RNA polymerase II. |
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Download this section (compressed HTML)Subunit of the heterodimeric FACT complex (Spt16p-Pob3p); FACT associates with chromatin via interaction with Nhp6Ap and Nhp6Bp, and reorganizes nucleosomes to facilitate access to DNA by RNA and DNA polymerases; specifically required for diauxic shift-induced H2B deposition onto rDNA genes; mutations cause reduced nucleosome occupancy over highly transcribed regions; coregulates transcription with Mot1p through preinitiation complex assembly and nucleosome organization
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