| Topic | Key finding | Evidence type (review/primary) | Source (short citation) | DOI/URL | Year |
|---|---|---|---|---|---|
| Identity and core function | **SET1/YHR119W (UniProt P38827)** in *Saccharomyces cerevisiae* is the sole H3K4-specific SET-domain histone methyltransferase in budding yeast and the catalytic subunit of COMPASS; it deposits H3K4me1, H3K4me2, and H3K4me3 on chromatin (pqac-00000010, pqac-00000012) | Review + primary | Deshpande & Bryk 2023; Woo et al. 2024 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1126/sciadv.adl6280 | Mar 2023; Jul 2024 |
| Reaction and substrate specificity | Set1/COMPASS catalyzes SAM-dependent methylation of **histone H3 Lys4**; canonical distribution is H3K4me3 at promoter/TSS-proximal regions, H3K4me2 in 5′ transcribed/coding regions, and H3K4me1 further downstream toward 3′ regions (pqac-00000000, pqac-00000018, pqac-00000020) | Primary + review | Woo et al. 2024; Serrano-Quílez & Rodriguez-Navarro 2025 | https://doi.org/10.1126/sciadv.adl6280 ; https://doi.org/10.1080/19491034.2025.2516909 | Jul 2024; Jun 2025 |
| COMPASS composition | Yeast COMPASS is an eight-subunit complex: Set1, Swd1/Cps50, Swd2/Cps35, Swd3/Cps30, Bre2/Cps60, Sdc1/Cps25, Spp1/Cps40, and Shg1/Cps15; the WRAD-like catalytic core includes Swd1, Swd3, Bre2, and Sdc1 (pqac-00000012, pqac-00000010) | Primary + review | Woo et al. 2024; Deshpande & Bryk 2023 | https://doi.org/10.1126/sciadv.adl6280 ; https://doi.org/10.1007/s00294-023-01265-3 | Jul 2024; Mar 2023 |
| COMPASS architecture and roles | Spp1 binds the **nSET** region and contributes particularly to H3K4me3; Swd2 is unique because it is both a COMPASS subunit and a CPF/3′-end processing factor; dimeric COMPASS supports symmetric H3K4me3 on nucleosomes (pqac-00000005, pqac-00000020, pqac-00000022) | Review + primary | Deshpande & Bryk 2023; Oh et al. 2024 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1186/s12915-024-01903-3 | Mar 2023; May 2024 |
| Pol II-coupled recruitment | Set1/COMPASS is recruited **co-transcriptionally** to active genes via interaction with the phosphorylated Rpb1 CTD; recent summaries emphasize Ser5-phosphorylated Pol II CTD and Set1 N-terminal/Swd2-dependent recruitment to 5′ gene regions (pqac-00000016, pqac-00000018) | Review + primary | Deshpande & Bryk 2023; Woo et al. 2024 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1126/sciadv.adl6280 | Mar 2023; Jul 2024 |
| H2Bub trans-histone crosstalk | H3K4 di- and tri-methylation by Set1/COMPASS depends on prior **H2BK123 monoubiquitination** by Rad6 (E2) and Bre1 (E3); this is a central trans-histone crosstalk pathway regulating H3K4me3 competence (pqac-00000001, pqac-00000002, pqac-00000021) | Review | Deshpande & Bryk 2023; Serrano-Quílez & Rodriguez-Navarro 2025 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1080/19491034.2025.2516909 | Mar 2023; Jun 2025 |
| Quantitative note on H2Bub | H2BK123ub is a low-abundance but critical activating signal for COMPASS; one review notes ubiquitinated H2B is **<10% of total H2B** in yeast, underscoring a tightly regulated modification with disproportionate functional impact (pqac-00000001) | Review | Serrano-Quílez & Rodriguez-Navarro 2025 | https://doi.org/10.1080/19491034.2025.2516909 | Jun 2025 |
| PAF1 complex input | The **PAF1 complex (Paf1, Ctr9, Rtf1, Leo1, Cdc73)** promotes H2BK123ub and thereby supports Set1-dependent H3K4 methylation; Rtf1 stimulates Rad6 activity and FACT helps PAF1 recruitment to transcribed chromatin (pqac-00000021, pqac-00000016) | Review | Serrano-Quílez & Rodriguez-Navarro 2025; Deshpande & Bryk 2023 | https://doi.org/10.1080/19491034.2025.2516909 ; https://doi.org/10.1007/s00294-023-01265-3 | Jun 2025; Mar 2023 |
| Bur1/2 kinase input | The **Bur1/Bur2 kinase complex** stimulates H2BK123ub by phosphorylating Rad6 at Ser120 and promoting PAF1C recruitment, thereby indirectly enhancing Set1-dependent H3K4 methylation (pqac-00000002, pqac-00000021) | Review | Deshpande & Bryk 2023; Serrano-Quílez & Rodriguez-Navarro 2025 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1080/19491034.2025.2516909 | Mar 2023; Jun 2025 |
| Swd2/Rad6 control of H3K4me3 | In a 2024 genome-wide analysis across **6020 protein-coding genes**, Rad6 catalytic activity was required for Swd2 chromatin binding; without Set1, Swd2 shifted from 5′ to 3′ regions, showing Set1 redistributes a limited Swd2 pool to promoter-proximal chromatin for H3K4me3 (pqac-00000004, pqac-00000007, pqac-00000022) | Primary | Oh et al. 2024 | https://doi.org/10.1186/s12915-024-01903-3 | May 2024 |
| NAT-dependent regulation | A 2024 study showed **NatA-mediated N-terminal acetylation** of Shg1, Spp1, and Swd2, and likely NatB action on Swd1, fine-tunes H3K4 methylation; deleting NatA substantially reduced global H3K4me3 and shifted H3K4me2 peaks toward promoters, while blocking Shg1 N-acetylation drastically reduced H3K4 methylation (pqac-00000000, pqac-00000012) | Primary | Woo et al. 2024 | https://doi.org/10.1126/sciadv.adl6280 | Jul 2024 |
| Nuclear/chromatin localization | Set1 functions on **nuclear chromatin** at actively transcribed genes; H3K4me3 and Set1 are enriched near promoter/TSS-proximal nucleosomes, with gradients beginning near nucleosome +1 and decaying downstream from promoters (pqac-00000017, pqac-00000018) | Primary + later synthesis | Woo et al. 2024; Luciano et al. 2026 | https://doi.org/10.1126/sciadv.adl6280 ; https://doi.org/10.1101/2025.11.23.690026 | Jul 2024; Apr 2026 |
| Transcriptional regulation | Expert synthesis in 2023-2024 emphasizes that Set1-dependent H3K4 methylation has **diverse and dynamic** roles in transcription, including promoter-associated activation, context-dependent repression, and coupling to transcriptional history through repeated Pol II passage (pqac-00000016, pqac-00000003) | Review | Deshpande & Bryk 2023; Yu & Lesch 2024 | https://doi.org/10.1007/s00294-023-01265-3 ; https://doi.org/10.1080/10985549.2024.2388254 | Mar 2023; Aug 2024 |
| Telomere maintenance | Set1 regulates telomere biology through both **H3K4 methylation-dependent and -independent** pathways: subtelomeric repression tracks strongly with H3K4 methylation, whereas telomere length maintenance appears to require Set1 catalytic/core function but is not strictly explained by H3K4 methylation status alone (pqac-00000024, pqac-00000025, pqac-00000029) | Primary | Jezek et al. 2023 | https://doi.org/10.1091/mbc.e22-06-0213 | Jan 2023 |
| Telomere phenotypes and factors | In set1Δ cells, telomeres are shortened and subtelomeric genes are derepressed; Set1 also calibrates abundance of telomere factors including **STN1, CDC13, EST1, EST3, TEN1, TLC1**, with both transcriptional and post-transcriptional effects (pqac-00000024, pqac-00000026, pqac-00000029) | Primary | Jezek et al. 2023 | https://doi.org/10.1091/mbc.e22-06-0213 | Jan 2023 |
| DNA double-strand break biology | Set1-dependent H3K4me3 accumulates near DSBs and declines with distance from the break; Set1 and H3K4me3 are recruited to damage sites, linking Set1 to chromatin-based DNA repair control (pqac-00000023) | Review | Deshpande & Bryk 2023 | https://doi.org/10.1007/s00294-023-01265-3 | Mar 2023 |
| Replication origin function | H3K4me2/3 deposited by Set1 are enriched at **origins of replication** and contribute to efficient DNA replication, extending Set1 function beyond transcription into DNA replication-associated chromatin control (pqac-00000023) | Review | Deshpande & Bryk 2023 | https://doi.org/10.1007/s00294-023-01265-3 | Mar 2023 |
| Recent expert view | Recent expert reviews argue that H3K4 methylation is not merely a passive mark of transcription but can directly shape chromatin openness and transcriptional activation in a context-dependent manner, with yeast Set1/COMPASS remaining a foundational mechanistic model (pqac-00000003, pqac-00000010) | Review | Yu & Lesch 2024; Deshpande & Bryk 2023 | https://doi.org/10.1080/10985549.2024.2388254 ; https://doi.org/10.1007/s00294-023-01265-3 | Aug 2024; Mar 2023 |


*Table: This table summarizes the key functional annotation points for Saccharomyces cerevisiae Set1/COMPASS, including its catalytic activity, complex composition, regulatory inputs, chromatin localization, and major biological roles. It highlights recent 2023-2024 evidence and provides DOI-linked sources for rapid verification.*