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

被引：34

作者：

Flury, Valentin ^{[1
,2
]}

Georgescu, Paula Raluca ^{[3
]}

Iesmantavicius, Vytautas ^{[1
,2
]}

Shimada, Yukiko ^{[1
,2
]}

Kuzdere, Tahsin ^{[1
]}

Braun, Sigurd ^{[3
]}

Buhler, Marc ^{[1
,2
]}

机构：

[1] Friedrich Miescher Inst Biomed Res, Maulbeerstr 66, CH-4058 Basel, Switzerland

[2] Univ Basel, Peterspl 10, CH-4003 Basel, Switzerland

[3] Ludwig Maximilians Univ Munchen, Biomed Ctr Munich, Physiol Chem, Grosshaderner Str 9, D-82152 Planegg Martinsried, Germany

来源：

MOLECULAR CELL | 2017年 / 67卷 / 02期

基金：

欧洲研究理事会;

关键词：

FISSION YEAST; SCHIZOSACCHAROMYCES-POMBE; H3K36; METHYLATION; RNA-POLYMERASE; TRANSCRIPTIONAL ELONGATION; SPURIOUS TRANSCRIPTION; MONOCLONAL-ANTIBODIES; CODING REGIONS; HP1; PROTEINS; HETEROCHROMATIN;

D O I：

10.1016/j.molcel.2017.05.026

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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.

引用

页码：294 / +

页数：23

共 70 条

[1] Structure and function of histone methylation binding proteins [J].