EP300 - morinlab/LLMPP GitHub Wiki
bibliography: 'morinlab.bib' csl: 'NLM.csl' link-citations: true nocite: | @rossiCodingGenomeSplenic2012, @veazeyCARM1InhibitionReduces2020, @nieGenomewideCRISPRScreens2021, @pasqualucciInactivatingMutationsAcetyltransferase2011,
Overview
Mutations in EP300 are significant contributors to the pathogenesis and progression of B-cell lymphomas such as DLBCL and FL.[@pasqualucciInactivatingMutationsAcetyltransferase2011] This gene has some recurrent sites of mutations (hot spots), which typically impact its HAT domain, a region crucial for acetylating histones and non-histone proteins.[@pasqualucciInactivatingMutationsAcetyltransferase2011]
Experimental Evidence
EP300 mutations impair histone acetylation, disrupt epigenetic gene regulation. Mutations in CREBBP and EP300 affect a common pathway and have been described as mutually exclusive due to some functional redundancy.[@pasqualucciInactivatingMutationsAcetyltransferase2011; @veazeyCARM1InhibitionReduces2020] Studies using genome-wide CRISPR-Cas9 screens have identified synthetic lethal interactions between CREBBP and EP300, suggesting that targeting one may affect the viability of cells with mutations in the other.[@nieGenomewideCRISPRScreens2021]
Relevance tier by entity
include:tables/table1_EP300.md
Mutation incidence in large patient cohorts (GAMBL reanalysis)
DLBCL
FL
Mutation pattern and selective pressure estimates
EP300 Hotspots
| Chromosome | Coordinate (hg19) | ref>alt | HGVSp |
|---|---|---|---|
| chr22 | 41566459 | T>C | Y1446H |
| chr22 | 41566460 | A>G | Y1446C |
| chr22 | 41566460 | A>C | Y1446S |
| chr22 | 41566462 | A>T | I1447F |
| chr22 | 41566466 | T>G | F1448C |
| chr22 | 41566474 | C>T | H1451Y |
| chr22 | 41566476 | T>G | H1451Q |
| chr22 | 41566478 | C>T | P1452L |
| chr22 | 41566486 | C>G | Q1455E |
| chr22 | 41566487 | A>G | Q1455R |
| chr22 | 41566488 | G>T | Q1455H |
| chr22 | 41566495 | C>T | P1458S |
| chr22 | 41566495 | C>A | P1458T |
| chr22 | 41566496 | C>T | P1458L |
| chr22 | 41566511 | T>C | L1463P |
| chr22 | 41566511 | T>G | L1463R |
| chr22 | 41566519 | T>G | W1466G |
| chr22 | 41566519 | T>A | W1466R |
| chr22 | 41566519 | T>C | W1466R |
| chr22 | 41566520 | G>T | W1466L |
| chr22 | 41566521 | G>C | W1466C |
| chr22 | 41566522 | T>A | Y1467N |
| chr22 | 41566522 | T>C | Y1467H |
| chr22 | 41566522 | T>G | Y1467D |
| chr22 | 41566523 | A>G | Y1467C |
| chr22 | 41566523 | A>T | Y1467F |
include:tables/browser_EP300.md
Expression
include:tables/mermaid_EP300.md