Transcription factor dimerization activates the p300 acetyltransferase

Esther Ortega, Srinivasan Rengachari, Ziad Ibrahim, Naghmeh Hoghoughi, Jonathan Gaucher, Alex S. Holehouse, Saadi Khochbin and Daniel Panne ()
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Esther Ortega: European Molecular Biology Laboratory
Srinivasan Rengachari: European Molecular Biology Laboratory
Ziad Ibrahim: European Molecular Biology Laboratory
Naghmeh Hoghoughi: CNRS UMR 5309, INSERM U1209, Université Grenoble Alpes, Institute for Advanced Biosciences
Jonathan Gaucher: European Molecular Biology Laboratory
Alex S. Holehouse: Washington University in St. Louis
Saadi Khochbin: CNRS UMR 5309, INSERM U1209, Université Grenoble Alpes, Institute for Advanced Biosciences
Daniel Panne: European Molecular Biology Laboratory

Nature, 2018, vol. 562, issue 7728, 538-544

Abstract: Abstract 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.

Keywords: IFN Regulatory Factor (IRF3); RING Domain; Chromatin Acetylation; Stimulator Of Interferon Genes (STING); IRF3 Activation (search for similar items in EconPapers)
Date: 2018
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Citations: View citations in EconPapers (9)

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DOI: 10.1038/s41586-018-0621-1

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