| Claim/finding | Mechanism/domain | Key assays/quantitative data | Source (authors, year, journal) | URL | Pub date |
|---|---|---|---|---|---|
| **Identity verified:** target is *Schizosaccharomyces pombe* Epe1/Jhd1, ORF **SPCC622.16c**, a JmjC-family chromatin regulator that localizes to heterochromatin via Swi6/HP1 rather than the budding-yeast Jhd1 KDM | JmjC-domain protein; heterochromatin-enriched through **Swi6/HP1** interaction; anti-silencing factor at centromeres, telomeres, mating-type locus | Localization/co-IP genetics place Epe1 at constitutive heterochromatin; loss causes spreading beyond boundaries and altered silencing; overexpression disrupts heterochromatin (pqac-00000001, pqac-00000004, pqac-00000007) | Isaac et al., 2007, *Genetics*; Raiymbek et al., 2020, *eLife* | https://doi.org/10.1534/genetics.106.068684 ; https://doi.org/10.7554/eLife.53155 | Apr 2007; Mar 2020 |
| Restricts heterochromatin spread and supports chromatin boundary function | Anti-silencing activity at heterochromatin edges; recruited by Swi6/HP1; function linked to JmjC integrity but not clearly to proven in vitro demethylation | **epe1Δ** enhances silencing at heterochromatin edges, promotes spreading across boundaries, partially suppresses clr defects, and causes broad transcriptional changes; classic phenotype is expansion of silent chromatin into neighboring euchromatin while also destabilizing normal heterochromatin domains (pqac-00000001, pqac-00000002) | Isaac et al., 2007, *Genetics*; Raiymbek et al., 2020, *eLife* | https://doi.org/10.1534/genetics.106.068684 ; https://doi.org/10.7554/eLife.53155 | Apr 2007; Mar 2020 |
| Dual role: prevention of ectopic heterochromatin is partly non-enzymatic, while removal of established ectopic H3K9me depends on the JmjC module | **N-terminal transcriptional activation (NTA) domain** prevents de novo ectopic H3K9me; **JmjC domain** contributes to erasure/removal of established H3K9 methylation | Sorida et al. define **NTA ~aa 1–171** (activity extending to ~208 aa) and a C-terminal Swi6-binding region **aa 487–948**; **H297A** JmjC mutant suppresses variegation/prevents de novo ectopic deposition but fails to efficiently remove established ectopic heterochromatin; single-copy Epe1 removes H3K9me at some loci, overexpression removes it more broadly (pqac-00000000, pqac-00000031) | Sorida et al., 2019, *PLOS Genetics* | https://doi.org/10.1371/journal.pgen.1008129 | Jun 2019 |
| Epe1 has strong non-enzymatic anti-silencing activity through methylation-dependent interaction with Swi6/HP1 and displacement of Clr3 HDAC | JmjC/cofactor-binding residues regulate conformation and **Swi6/HP1** binding; **C-terminus** directly binds Swi6; Epe1-Swi6 complex antagonizes **Clr3**-mediated hypoacetylation | Purified Epe1 showed **no detectable H3K9 demethylase activity in vitro**; JmjC cofactor mutants (**H297A, Y307A, Y370A**) lose Swi6 binding/localization; Epe1 C-terminus is sufficient to displace **Clr3** from heterochromatin and disrupt silencing (pqac-00000002, pqac-00000003, pqac-00000004, pqac-00000006, pqac-00000007) | Raiymbek et al., 2020, *eLife* | https://doi.org/10.7554/eLife.53155 | Mar 2020 |
| cAMP-PKA signaling regulates Epe1 abundance mainly at the **translation** step, linking nutrient signaling to heterochromatin state | **Git3/Gpa/Cyr1 → cAMP → Pka1** promotes efficient translation of **epe1+ mRNA**; effect is post-transcriptional and largely independent of altered protein degradation | In **git3Δ**, polysome-associated **epe1+ mRNA** is **nearly abolished**; **git3Δ cgs1Δ** partially restores polysome loading; cycloheximide chase shows similar Epe1 degradation over **45 min**, arguing against stability control; low glucose for **6 h** lowers Epe1 protein and increases H3K9me2 at many heterochromatin islands; **SacI::ade6+** silencing in git3Δ gives red/pink colonies but weaker than **epe1Δ** (pqac-00000016, pqac-00000019, pqac-00000020, pqac-00000022, pqac-00000023) | Bao et al., 2022, *PLOS Genetics* | https://doi.org/10.1371/journal.pgen.1010049 | Feb 2022 |
| Stress triggers proteasome-dependent Epe1 truncation to **tEpe1**, reducing nuclear/chromatin association and promoting adaptive H3K9 methylation | Regulated ubiquitin/proteasome processing removes **~N-terminal 150 aa**; requires **cell integrity pathway (CIP) MAPK** components **Pek1/Pmk1**; truncated protein accumulates more in cytoplasm | tEpe1 appears after ~**7 h** at **14 mM caffeine** and after **16 h** at **5–15 mM** caffeine; disappears ~**9 h** after caffeine removal; cleavage signal maps to **aa 100–150**, and deleting **aa 101–110** blocks cleavage; proteomics found **23 proteasome subunits** enriched with Epe1 after caffeine; **8/10** caffeine-resistant **Epe1ΔN150** isolates showed higher H3K9me2 at **isl14/ncRNA394**; resistance quantified as resistant colonies per **1×10^4** viable cells plated (pqac-00000008, pqac-00000009, pqac-00000011, pqac-00000012, pqac-00000014, pqac-00000015) | Yaseen et al., 2022, *Nature Structural & Molecular Biology* | https://doi.org/10.1038/s41594-022-00801-y | Jul 2022 |
| 2024 work shows rapid Epe1 loss can drive multi-day epigenetic adaptation and short-term memory of heterochromatin misregulation | Acute Epe1 depletion unleashes H3K9me spreading; adaptive silencing targets **clr4+** and nearby loci; memory depends on residual H3K9 methylation and is modulated by chromatin factors such as **Red1** and **Gcn5** | Inducible **epe1deg** gives complete loss of detectable protein within **~30 min** and ~**8-fold** mRNA reduction; in **mst2Δ epe1deg**, **clr4+ mRNA** falls ~**4-fold**; stress phase spans **24–48 h**, adaptation evident by ~**120 h**; short recovery of **24 h** preserves partial memory, whereas **48–72 h** recovery erases it; colony area stats: **0 h 34.5 ± 27.3**, **120 h 118.9 ± 37.6**, **144 h 87.3 ± 59.4**, **168 h 26.3 ± 25.9 pixels²**; adaptive memory persists ~**24 h (~6–8 generations)** after stress removal (pqac-00000024, pqac-00000025, pqac-00000026, pqac-00000027, pqac-00000028, pqac-00000029, pqac-00000030) | Larkin et al., 2024, *Developmental Cell* | https://doi.org/10.1016/j.devcel.2024.07.006 | Aug 2024 |
| 2024 FACT engineering study shows stronger FACT recruitment can suppress **epe1Δ**-associated heterochromatin variegation | **Pob3-Nhp6 fusion [PN(x3)]** enhances FACT chromatin binding, histone-turnover repression, H3K9 methylation, and Swi6 enrichment; FACT acts upstream of Epe1-linked variegation | On **dg::ade6+**, **epe1Δ** showed silencing defect in **~40%** of colonies (pink/white); **pn(x3)** strongly suppressed this variegation; ChIP at pericentromeric **imr/dh** showed **2–3-fold** increases in **H3K9me** and **HP1/Swi6** with **pn(x3)**; colony scoring used ~**400 colonies/condition**, with ChIP typically **n=3** (pqac-00000032, pqac-00000033, pqac-00000035) | Takahata et al., 2024, *Genes to Cells* | https://doi.org/10.1111/gtc.13132 | Jun 2024 |


*Table: This table compiles key functional-annotation evidence for Schizosaccharomyces pombe Epe1/Jhd1 (UniProt O94603), including mechanism, localization, pathway context, and the most informative quantitative results. It is useful as a citation-ready summary spanning foundational studies through 2024 advances.*