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

Molecular cell | 2017

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.

Pubmed ID: 28648780 RIS Download

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This is a list of tools and resources that we have found mentioned in this publication.


Histone H3 antibody (antibody)

RRID:AB_2687473

This monoclonal targets Histone H3

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Ubiquityl-Histone H2B (Lys120) (D11) XP Rabbit mAb (antibody)

RRID:AB_10693452

This monoclonal targets Ubiquityl-Histone H2B (Lys120) (D11) XP Rabbit mAb

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Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

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H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

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Anti-Histone H3 (tri methyl K4) antibody - ChIP Grade (antibody)

RRID:AB_306649

This polyclonal targets Histone H3 (tri methyl K4)

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Histone H2B antibody (pAb) (antibody)

RRID:AB_2631110

This polyclonal targets H2B

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H3K36me3-human (antibody)

RRID:AB_306966

This polyclonal targets H3K36me3

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H3K14ac-human (antibody)

RRID:AB_880442

This monoclonal targets H3K14ac

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QUASR (software resource)

RRID:SCR_006820

A lightweight software pipeline written to process and analyse next-generation sequencing (NGS) data from Illumina, 454, and Ion Torrent platforms. Although originally written for viral data, it is generic enough to work on any NGS dataset. Functions include: duplicate removal, demultiplexing, primer-removal, quality-assurance (QA) graphing, quality control (QC), consensus-generation, minority-variant determination, minority-variant graphing.

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R Manuals (data or information resource)

RRID:SCR_000036

Manuals for R created on Debian Linux that can be downloaded as PDF files, EPUB files (for R-devel and R-patched), or directly browsed as HTML. They may differ from the manuals for Mac or Windows on platform-specific pages, but most parts will be identical for all platforms.

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ImageJ (software resource)

RRID:SCR_003070

Open source Java based image processing software program designed for scientific multidimensional images. ImageJ has been transformed to ImageJ2 application to improve data engine to be sufficient to analyze modern datasets.

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Goat Anti-Mouse IgG (H L)-HRP Conjugate (antibody)

RRID:AB_11125547

This unknown targets Goat Mouse IgG (H L)-HRP Conjugate

View all literature mentions

Anti-Histone H3 (tri methyl K4) antibody - ChIP Grade (antibody)

RRID:AB_306649

This polyclonal targets Histone H3 (tri methyl K4)

View all literature mentions

H3K36me3-human (antibody)

RRID:AB_306966

This polyclonal targets H3K36me3

View all literature mentions

H3K14ac-human (antibody)

RRID:AB_880442

This monoclonal targets H3K14ac

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Histone H2B antibody (pAb) (antibody)

RRID:AB_2631110

This polyclonal targets H2B

View all literature mentions

H3-celegans (antibody)

RRID:AB_302613

This polyclonal targets H3

View all literature mentions