Transcription factor dimerization activates the p300 acetyltransferase,Nature

当前位置： X-MOL 学术 › Nature › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

Transcription factor dimerization activates the p300 acetyltransferase
Nature ( IF 50.5 ) Pub Date : 2018-10-01 , DOI: 10.1038/s41586-018-0621-1
Esther Ortega ₁ , Srinivasan Rengachari _{1,

2} , Ziad Ibrahim _{1,

3} , Naghmeh Hoghoughi ₄ , Jonathan Gaucher _{1,

5} , Alex S Holehouse ₆ , Saadi Khochbin ₄ , Daniel Panne _{1,

3}

Affiliation

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.The activation of the histone acetyltransferase p300 depends on the activation and oligomerization status of transcription factor ligands.

中文翻译：

转录因子二聚化激活 p300 乙酰转移酶

转录共激活因子 p300 是一种组蛋白乙酰转移酶 (HAT)，通常被招募到转录增强子并通过乙酰化染色质来调节基因表达。在这里，我们表明 p300 的激活直接取决于转录因子配体的激活和寡聚化状态。使用两个模型转录因子 IRF3 和 STAT1，我们证明转录因子二聚化使 p300 在高度保守和内在无序的富含赖氨酸的自抑制环中发生反式自动乙酰化，从而导致 p300 激活。我们描述了 p300 的晶体结构，其中自抑制环侵入相邻 HAT 结构域的活性位点，揭示了反式自乙酰化反应中间体的快照。对活性位点的底物访问涉及自抑制环结构域的重排。我们的数据解释了细胞信号传导和转录因子的激活和二聚化如何控制 p300 的激活，从而解释了为什么基因转录与染色质乙酰化有关。组蛋白乙酰转移酶 p300 的激活取决于转录因子配体的激活和寡聚化状态.

更新日期：2018-10-01

点击分享查看原文

点击收藏

公开下载

阅读更多本刊最新论文本刊介绍/投稿指南11