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  The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1

Flury, V., Georgescu, P. R., Iesmantavicius, V., Shimada, Y., Kuzdere, T., Braun, S., et al. (2017). The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. Molecular Cell, 67, 294-307. doi:10.1016/j.molcel.2017.05.026.

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Item Permalink: https://hdl.handle.net/21.11116/0000-000F-44A5-A Version Permalink: https://hdl.handle.net/21.11116/0000-000F-44A6-9
Genre: Journal Article

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10.1016_j.molcel.2017.05.026.pdf (Publisher version), 5MB
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https://hdl.handle.net/21.11116/0000-000F-44A7-8
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10.1016_j.molcel.2017.05.026.pdf
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2017
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The Author(s). Published by Elsevier Inc. All rights reserved.
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https://www.sciencedirect.com/science/article/pii/S1097276517303660?via%3Dihub (Publisher version)
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 Creators:
Flury, Valentin1, Author           
Georgescu, Paula Raluca2, Author
Iesmantavicius, Vytautas2, Author
Shimada, Yukiko2, Author
Kuzdere, Tahsin2, Author
Braun, Sigurd2, Author
Bühler, Marc2, Author
Affiliations:
1Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243641              
2External Organizations, ou_persistent22              

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Free keywords: Brl1/BRE1; Gcn5; H2B ubiquitin; H3K36me3; Mst2; RNA interference; acetylomics; epigenetic gene silencing; heterochromatin; histone modification.
 Abstract: Faithful propagation of functionally distinct chromatin states is crucial for maintaining cellular identity, and its breakdown can lead to diseases such as cancer. Whereas mechanisms that sustain repressed states have been intensely studied, regulatory circuits that protect active chromatin from inactivating signals are not well understood. Here we report a positive feedback loop that preserves the transcription-competent state of RNA polymerase II-transcribed genes. We found that Pdp3 recruits the histone acetyltransferase Mst2 to H3K36me3-marked chromatin. Thereby, Mst2 binds to all transcriptionally active regions genome-wide. Besides acetylating histone H3K14, Mst2 also acetylates Brl1, a component of the histone H2B ubiquitin ligase complex. Brl1 acetylation increases histone H2B ubiquitination, which positively feeds back on transcription and prevents ectopic heterochromatin assembly. Our work uncovers a molecular pathway that secures epigenome integrity and highlights the importance of opposing feedback loops for the partitioning of chromatin into transcriptionally active and inactive states.

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Language(s): eng - English
 Dates: 2017-07-20
 Publication Status: Published online
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: DOI: 10.1016/j.molcel.2017.05.026
 Degree: -

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Title: Molecular Cell
Source Genre: Journal
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Publ. Info: Cambridge, Mass. : Cell Press
Pages: - Volume / Issue: 67 Sequence Number: - Start / End Page: 294 - 307 Identifier: ISSN: 1097-2765
CoNE: https://pure.mpg.de/cone/journals/resource/954925610929