| RRC ID |
72243
|
| 著者 |
Fujimoto M, Takii R, Matsumoto M, Okada M, Nakayama KI, Nakato R, Fujiki K, Shirahige K, Nakai A.
|
| タイトル |
HSF1 phosphorylation establishes an active chromatin state via the TRRAP-TIP60 complex and promotes tumorigenesis.
|
| ジャーナル |
Nat Commun
|
| Abstract |
Transcriptional regulation by RNA polymerase II is associated with changes in chromatin structure. Activated and promoter-bound heat shock transcription factor 1 (HSF1) recruits transcriptional co-activators, including histone-modifying enzymes; however, the mechanisms underlying chromatin opening remain unclear. Here, we demonstrate that HSF1 recruits the TRRAP-TIP60 acetyltransferase complex in HSP72 promoter during heat shock in a manner dependent on phosphorylation of HSF1-S419. TRIM33, a bromodomain-containing ubiquitin ligase, is then recruited to the promoter by interactions with HSF1 and a TIP60-mediated acetylation mark, and cooperates with the related factor TRIM24 for mono-ubiquitination of histone H2B on K120. These changes in histone modifications are triggered by phosphorylation of HSF1-S419 via PLK1, and stabilize the HSF1-transcription complex in HSP72 promoter. Furthermore, HSF1-S419 phosphorylation is constitutively enhanced in and promotes proliferation of melanoma cells. Our results provide mechanisms for HSF1 phosphorylation-dependent establishment of an active chromatin status, which is important for tumorigenesis.
|
| 巻・号 |
13(1)
|
| ページ |
4355
|
| 公開日 |
2022-7-29
|
| DOI |
10.1038/s41467-022-32034-4
|
| PII |
10.1038/s41467-022-32034-4
|
| PMID |
35906200
|
| PMC |
PMC9338313
|
| MeSH |
Adaptor Proteins, Signal Transducing / metabolism
Carcinogenesis / genetics
Chromatin*
Heat Shock Transcription Factors / genetics
Heat Shock Transcription Factors / metabolism
Histones* / metabolism
Humans
Lysine Acetyltransferase 5 / metabolism
Nuclear Proteins / metabolism
Phosphorylation
Protein Binding
Transcription Factors / genetics
|
| IF |
12.121
|
| リソース情報 |
| ヒト・動物細胞 |
MMAc(RCB0808)
MCF7(RCB1904)
Hep G2(RCB1648)
HCT116(RCB2979)
A549(RCB0098)
LNCap.FGC(RCB2144)
PANC-1(RCB2095) |
