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

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The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. / Flury, Valentin; Georgescu, Paula Raluca; Iesmantavicius, Vytautas; Shimada, Yukiko; Kuzdere, Tahsin; Braun, Sigurd; Bühler, Marc.

In: Molecular Cell, Vol. 67, No. 2, 2017, p. 294-307.e9.

Research output: Contribution to journal › Journal article › Research › peer-review

Harvard

Flury, V, Georgescu, PR, Iesmantavicius, V, Shimada, Y, Kuzdere, T, Braun, S & Bühler, M 2017, 'The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1', Molecular Cell, vol. 67, no. 2, pp. 294-307.e9. https://doi.org/10.1016/j.molcel.2017.05.026

APA

Flury, V., Georgescu, P. R., Iesmantavicius, V., Shimada, Y., Kuzdere, T., Braun, S., & Bühler, M. (2017). The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. Molecular Cell, 67(2), 294-307.e9. https://doi.org/10.1016/j.molcel.2017.05.026

Vancouver

Flury V, Georgescu PR, Iesmantavicius V, Shimada Y, Kuzdere T, Braun S et al. The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. Molecular Cell. 2017;67(2):294-307.e9. https://doi.org/10.1016/j.molcel.2017.05.026

Author

Flury, Valentin ; Georgescu, Paula Raluca ; Iesmantavicius, Vytautas ; Shimada, Yukiko ; Kuzdere, Tahsin ; Braun, Sigurd ; Bühler, Marc. / The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1. In: Molecular Cell. 2017 ; Vol. 67, No. 2. pp. 294-307.e9.

Bibtex

@article{1fe5409776e94ff0851052740f170ac2,
title = "The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1",
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.",
keywords = "acetylomics, Brl1/BRE1, epigenetic gene silencing, Gcn5, H2B ubiquitin, H3K36me3, heterochromatin, histone modification, Mst2, RNA interference",
author = "Valentin Flury and Georgescu, {Paula Raluca} and Vytautas Iesmantavicius and Yukiko Shimada and Tahsin Kuzdere and Sigurd Braun and Marc B{\"u}hler",
note = "Publisher Copyright: {\textcopyright} 2017 The Author(s)",
year = "2017",
doi = "10.1016/j.molcel.2017.05.026",
language = "English",
volume = "67",
pages = "294--307.e9",
journal = "Molecular Cell",
issn = "1097-2765",
publisher = "Cell Press",
number = "2",

}

RIS

TY - JOUR

T1 - The Histone Acetyltransferase Mst2 Protects Active Chromatin from Epigenetic Silencing by Acetylating the Ubiquitin Ligase Brl1

AU - Flury, Valentin

AU - Georgescu, Paula Raluca

AU - Iesmantavicius, Vytautas

AU - Shimada, Yukiko

AU - Kuzdere, Tahsin

AU - Braun, Sigurd

AU - Bühler, Marc

N1 - Publisher Copyright: © 2017 The Author(s)

PY - 2017

Y1 - 2017

N2 - 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.

AB - 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.

KW - acetylomics

KW - Brl1/BRE1

KW - epigenetic gene silencing

KW - Gcn5

KW - H2B ubiquitin

KW - H3K36me3

KW - heterochromatin

KW - histone modification

KW - Mst2

KW - RNA interference

U2 - 10.1016/j.molcel.2017.05.026

DO - 10.1016/j.molcel.2017.05.026

M3 - Journal article

C2 - 28648780

AN - SCOPUS:85021137961

VL - 67

SP - 294-307.e9

JO - Molecular Cell

JF - Molecular Cell

SN - 1097-2765

IS - 2

ER -

ID: 337388128