| Aspect | Key findings (1-2 sentences) | Evidence type | Key papers with year and URL |
|---|---|---|---|
| Identity & complex (SAS-I) | **S. cerevisiae** SAS2 (UniProt P40963) matches the yeast **MYST-family histone acetyltransferase** Sas2, the catalytic subunit of the **SAS-I complex** with Sas4 and Sas5. This distinguishes it from related but different MYST proteins such as Esa1, Sas3, and metazoan MOF homologs. (pqac-00000001, pqac-00000002, pqac-00000004) | biochemical, genetic | Meijsing & Ehrenhofer-Murray 2001 — https://doi.org/10.1101/gad.929001; Heise et al. 2012 — https://doi.org/10.1093/nar/gkr649 |
| Enzymatic reaction / substrate | Sas2 is a histone acetyltransferase with an **acetyl-CoA-binding HAT domain**; HAT chemistry transfers an acetyl group from **acetyl-CoA** to lysine ε-amino groups. Genetic and chromatin evidence support **histone H4 Lys16 (H4K16)** as the principal in vivo Sas2/SAS-I target; SAS-I supplies about **60% of cellular H4K16ac**. (pqac-00000015, pqac-00000016, pqac-00000018, pqac-00000020) | biochemical, genetic | Meijsing & Ehrenhofer-Murray 2001 — https://doi.org/10.1101/gad.929001; Boltengagen et al. 2021 — https://doi.org/10.1371/journal.pone.0251660; Reiter et al. 2015 — https://doi.org/10.1093/femsyr/fov073 |
| Localization | Sas2 is a **chromatin-bound nuclear protein**; GFP-tagging showed predominant **nuclear localization including the nucleolus**, and ChIP detected association with **rDNA**. Functionally, Sas2 activity is also evident at **telomeres, HM loci, subtelomeres, and ORFs**. (pqac-00000015, pqac-00000014, pqac-00000013) | biochemical, genetic, genome-wide | Meijsing & Ehrenhofer-Murray 2001 — https://doi.org/10.1101/gad.929001; Heise et al. 2012 — https://doi.org/10.1093/nar/gkr649 |
| Role in heterochromatin boundary & silencing | Sas2-mediated **H4K16 acetylation antagonizes SIR binding/spreading**, helping define **subtelomeric and HMR boundary states** and supporting proper silencing architecture. Loss of SAS-I reduces H4K16ac and permits inappropriate **subtelomeric SIR spreading** and altered silencing at telomeres/HM loci/rDNA. (pqac-00000000, pqac-00000013, pqac-00000017) | genetic, genome-wide | Boltengagen et al. 2021 — https://doi.org/10.1371/journal.pone.0251660; Heise et al. 2012 — https://doi.org/10.1093/nar/gkr649 |
| Replication-coupled deposition | SAS-I interacts with **CAF-I/Cac1 and Asf1**, linking Sas2 to chromatin assembly after replication. H4K16ac appears **immediately upon replication** in a SAS-I-dependent manner, supporting a model in which Sas2 acetylates newly assembled chromatin during **S phase**. (pqac-00000003, pqac-00000016, pqac-00000019) | genetic, biochemical, genome-wide | Meijsing & Ehrenhofer-Murray 2001 — https://doi.org/10.1101/gad.929001; Boltengagen et al. 2021 — https://doi.org/10.1371/journal.pone.0251660; Reiter 2014 — https://doi.org/10.18452/17041 |
| Genome-wide distribution | Genome-wide mapping showed Sas2-dependent H4K16ac is strongest across the **bodies of many ORFs**, especially **lowly transcribed genes**, with less effect in intergenic regions. Sas2-dependent deposition occurs broadly and can be **independent of transcription and histone exchange**. (pqac-00000013, pqac-00000017, pqac-00000018) | genome-wide | Heise et al. 2012 — https://doi.org/10.1093/nar/gkr649; Reiter et al. 2015 — https://doi.org/10.1093/femsyr/fov073 |
| 2024 IMD2 heterochromatin fluctuation findings | At the subtelomeric **IMD2** locus, 2024 single-cell work showed repeated switching between ON/OFF expression states under GTP depletion conditions, and about **30% of cells** consistently expressed IMD2; figure-level summaries indicated roughly **20-23%** of tracked lineages remained consistently ON in one analysis. These studies place IMD2 boundary behavior in the context of Sas2/H4K16ac-defined heterochromatin boundaries and identify additional HAT-related factors such as **Spt8/SAGA** affecting IMD2 regulation; **spt8Δ** reduced transcription about **3-fold** in the cited assay. (pqac-00000008, pqac-00000011, pqac-00000012, pqac-00000021) | single-cell, genetic | Ayano et al. 2024 — https://doi.org/10.1111/gtc.13094; Ayano & Oki 2024 — https://doi.org/10.1266/ggs.23-00284 |
| 2024 modeling work | A 2024 **PNAS** study modeled **two-way feedback** between chromatin compaction and histone modification state at **HMR**, incorporating acetylation-dependent locus size and Sir-mediated feedback. The framework reproduced prior quantitative silencing dynamics and provides a current mechanistic interpretation for how marks such as **H4K16ac** help generate **bistable heterochromatin states**. (pqac-00000009, pqac-00000010) | modeling | Miangolarra et al. 2024 — https://doi.org/10.1073/pnas.2403316121 |


*Table: This table summarizes the core functional annotation of S. cerevisiae SAS2/P40963, including its biochemical role, localization, chromatin functions, and the most relevant recent 2024 findings. It is useful as a compact evidence map linking major claims to specific study types and papers.*