| Annotation aspect | Summary for yeast DOT1 (Q04089 / YDR440W) | Key quantitative values | Citations |
|---|---|---|---|
| Identity / core definition | DOT1 encodes the conserved, non-SET histone lysine methyltransferase Dot1p (KMT4), originally identified as a disruptor of telomeric silencing; it is the sole H3K79 methyltransferase in *S. cerevisiae*. | Dot1 loss causes complete loss of H3K79 methylation; ~90% of the *S. cerevisiae* genome is reported to carry H3K79 methylation. | (pqac-00000003, pqac-00000004, pqac-00000007) |
| Reaction catalyzed | Dot1 transfers methyl groups from S-adenosyl-L-methionine (SAM/AdoMet) to histone H3 Lys79, generating H3K79me1, H3K79me2, and H3K79me3; catalysis is distributive/non-processive rather than processive. | H3K79me1 and H3K79me2 half-lives reported in HeLa for the conserved mark are ~1.105 and ~3.609 days, illustrating mark stability in the absence of a known demethylase. | (pqac-00000002, pqac-00000003, pqac-00000005, pqac-00000007) |
| Substrate specificity | Dot1 acts on chromatin/nucleosomes and does not methylate free histone H3 or free histones efficiently; the relevant substrate is nucleosomal H3K79 in the globular core exposed on the nucleosome surface. | Binding affinity is similar for unmodified vs H4K16ac nucleosomes: Kd 70.8 ± 6.5 nM vs 83.3 ± 15.0 nM. | (pqac-00000002, pqac-00000005, pqac-00000006, pqac-00000013) |
| Regulation by H2B-K123 ubiquitination | Efficient H3K79 di-/trimethylation requires prior H2B-K123 monoubiquitination by Rad6/Bre1; mutating H2BK123 or deleting Rad6 strongly impairs H3K79 methylation. Paf1 complex helps couple this pathway to elongating RNAPII by promoting Rad6/Bre1 recruitment. | On unmodified nucleosomes, Km = 381 ± 227 nM and kcat = 0.85 ± 0.21 min⁻¹; on H2Bub nucleosomes, Km = 387 ± 59.2 nM and kcat = 9.71 ± 0.54 min⁻¹. Dot1 overexpression increased H2Bub1 with ***P < 0.001 in tested backgrounds. | (pqac-00000002, pqac-00000006, pqac-00000009, pqac-00000013) |
| Regulation by H4K16 acetylation | H4K16ac directly and allosterically stimulates Dot1; the effect is specific to H4K16ac and cooperates with H2Bub. Loss of Sas2/H4K16ac or H4K16 mutation reduces higher H3K79 methyl states and alters Dot1 chromatin distribution. | H4K16ac nucleosomes: Km = 264 ± 40.0 nM, kcat = 17.5 ± 0.88 min⁻¹; doubly modified H4K16ac/H2Bub nucleosomes: Km = 456 ± 46.5 nM, kcat = 35.5 ± 1.37 min⁻¹. Kd remains similar to unmodified nucleosomes, indicating stimulation is catalytic more than binding-driven. | (pqac-00000001, pqac-00000004, pqac-00000005, pqac-00000013) |
| Regulation by Rpd3/HDAC crosstalk | Histone deacetylation opposes Dot1 activity at a subset of genes; budding yeast Rpd3 restricts H3K79 methylation, and analogous HDAC1-DOT1L antagonism is conserved in mammals. | Yeast evidence identifies Rpd3 as a negative regulator of Dot1 and explains absence of H3K79me3 at a subset of genes, though no single fold-change value is provided in the extracted text. | (pqac-00000004) |
| Telomeric silencing / Sir antagonism | Dot1/H3K79 methylation antagonizes Sir protein spreading: H3K79 methylation blocks Sir3 binding, whereas Dot1 loss or H3K79 mutation impairs telomeric silencing by mislocalizing Sir proteins; Dot1 overexpression spreads H3K79 methylation into silent chromatin. | Quantitative extracted text is limited, but the phenotype is robust enough that Dot1 was named for disruption of telomeric silencing. | (pqac-00000000, pqac-00000004, pqac-00000006, pqac-00000012) |
| Transcription / elongation coupling | H3K79 methylation correlates strongly with transcriptional activity, is enriched in transcribed regions, and is functionally linked to elongation complexes and Paf1C-Rad6/Bre1-mediated cotranscriptional chromatin modification. Dot1 can act as activator or repressor depending on context. | ~90% genome methylation reported; long genes show higher H3K79me3, whereas 0.5–1 kb genes show relatively higher H3K79me1. | (pqac-00000000, pqac-00000004, pqac-00000005, pqac-00000008) |
| DNA damage response / checkpoints | Dot1/H3K79 methylation contributes to genome stability and checkpoint signaling; Dot1 or H3K79 defects impair recruitment of DNA damage factors and cause defects in G1 and intra-S checkpoint responses after ionizing radiation. | Extracted evidence is strong mechanistically but does not provide a numerical effect size in the available contexts. | (pqac-00000000, pqac-00000007) |
| Nucleosome dynamics / histone exchange | Beyond catalysis, Dot1 has methylation-independent histone chaperone activity, can assemble nucleosomes, and regulates histone exchange/chromatin accessibility in transcribed regions, particularly long genes; this helps balance Set2-Rpd3S effects. | Histone exchange decreased at centers of long genes >2 kb (n = 1325) and 1–2 kb genes (n = 2266) in dot1Δ, but slightly increased for 0.5–1 kb genes (n = 1600). ATAC-seq/accessibility analyses used n = 2189 genes; genome-wide transcribed-region analysis covered n = 6692 genes; significance commonly ***P < 0.001. | (pqac-00000005, pqac-00000008, pqac-00000010, pqac-00000011) |
| Localization | Functionally, Dot1 is nuclear/chromatin-associated, acting on nucleosomes across euchromatic transcribed regions and at boundaries of silent chromatin such as telomeres. | Localization is inferred from chromatin binding and genome-wide distribution rather than a single compartment-specific quantitative assay in the extracted evidence. | (pqac-00000000, pqac-00000004, pqac-00000005) |


*Table: This table condenses the core functional annotation of yeast DOT1 (UniProt Q04089), including its enzymatic activity, chromatin substrate specificity, key regulatory crosstalk, principal biological roles, and the most useful quantitative values extracted from the available evidence.*