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DOI | 10.1038/s41586-018-0240-x |
Transcription factor dimerization activates the p300 acetyltransferase | |
Ortega, Esther1; Rengachari, Srinivasan1,6; Ibrahim, Ziad1,2; Hoghoughi, Naghmeh3; Gaucher, Jonathan1,7; Holehouse, Alex S.4,5; Khochbin, Saadi3; Panne, Daniel1,2 | |
2018-10-25 | |
发表期刊 | NATURE
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ISSN | 0028-0836 |
EISSN | 1476-4687 |
出版年 | 2018 |
卷号 | 562期号:7728页码:538-+ |
文章类型 | Article |
语种 | 英语 |
国家 | France; England; USA; Germany |
英文摘要 | The transcriptional co-activator p300 is a histone acetyltransferase (HAT) that is typically recruited to transcriptional enhancers and regulates gene expression by acetylating chromatin. Here we show that the activation of p300 directly depends on the activation and oligomerization status of transcription factor ligands. Using two model transcription factors, IRF3 and STAT1, we demonstrate that transcription factor dimerization enables the trans-autoacetylation of p300 in a highly conserved and intrinsically disordered autoinhibitory lysine-rich loop, resulting in p300 activation. We describe a crystal structure of p300 in which the autoinhibitory loop invades the active site of a neighbouring HAT domain, revealing a snapshot of a trans-autoacetylation reaction intermediate. Substrate access to the active site involves the rearrangement of an autoinhibitory RING domain. Our data explain how cellular signalling and the activation and dimerization of transcription factors control the activation of p300, and therefore explain why gene transcription is associated with chromatin acetylation. |
领域 | 地球科学 ; 气候变化 ; 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000448277800048 |
WOS关键词 | CRYSTAL-STRUCTURE ; STRUCTURAL BASIS ; HISTONE ACETYLATION ; INTERFERON-GAMMA ; CATALYTIC CORE ; GENOME-WIDE ; CBP ; DNA ; RECRUITMENT ; CBP/P300 |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/202917 |
专题 | 地球科学 资源环境科学 气候变化 |
作者单位 | 1.European Mol Biol Lab, Grenoble, France; 2.Univ Leicester, Leicester Inst Struct & Chem Biol, Dept Mol & Cell Biol, Leicester, Leics, England; 3.Univ Grenoble Alpes, Inst Adv Biosci, CNRS UMR 5309, INSERM U1209, Grenoble, France; 4.Washington Univ, Dept Biomed Engn, St Louis, MO USA; 5.Washington Univ, Ctr Biol Syst Engn, St Louis, MO USA; 6.Max Planck Inst Biophys Chem, Dept Mol Biol, Gottingen, Germany; 7.Univ Grenoble Alpes, INSERM U1042, Lab HP2, Grenoble, France |
推荐引用方式 GB/T 7714 | Ortega, Esther,Rengachari, Srinivasan,Ibrahim, Ziad,et al. Transcription factor dimerization activates the p300 acetyltransferase[J]. NATURE,2018,562(7728):538-+. |
APA | Ortega, Esther.,Rengachari, Srinivasan.,Ibrahim, Ziad.,Hoghoughi, Naghmeh.,Gaucher, Jonathan.,...&Panne, Daniel.(2018).Transcription factor dimerization activates the p300 acetyltransferase.NATURE,562(7728),538-+. |
MLA | Ortega, Esther,et al."Transcription factor dimerization activates the p300 acetyltransferase".NATURE 562.7728(2018):538-+. |
条目包含的文件 | 条目无相关文件。 |
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