The H3K36me2 methyltransferase NSD1 modulates H3K27ac at active enhancers to safeguard gene expression.

Nucleic Acids Research
Yuan FangDong Fang

Abstract

Epigenetics, especially histone marks, functions beyond the DNA sequences to regulate gene expression. Depletion of NSD1, which catalyzes H3K36me2, leads to both up- and down-regulation of gene expression, indicating NSD1 is associated with both active and repressed gene expression. It's known that NSD1 regulates the deposition and expansion of H3K27me3, a repressive mark for gene expression, to keep active gene transcription. However, how NSD1 functions to repress gene expression is largely unknown. Here, we find that, when NSD1 is knocked out in mouse embryonic stem cells (mESCs), H3K27ac increases correlatively with the decrease of H3K36me2 at active enhancers, which is associated with mesoderm differentiation genes, leading to elevated gene expression. Mechanistically, NSD1 recruits HDAC1, the deacetylase of H3K27ac, to chromatin. Moreover, HDAC1 knockout (KO) recapitulates the increase of H3K27ac at active enhancers as the NSD1 depletion. Together, we propose that NSD1 deposits H3K36me2 and recruits HDAC1 at active enhancers to serve as a 'safeguard', preventing further activation of active enhancer-associated genes.

References

Jan 19, 2000·Nature·B D Strahl, C D Allis
Aug 11, 2001·Science·T Jenuwein, C D Allis
Feb 13, 2002·Molecular and Cellular Biology·Brian D StrahlC David Allis
Mar 16, 2002·Nature Genetics·Naohiro KurotakiNaomichi Matsumoto
Nov 7, 2002·Cell·Theodora AgaliotiDimitris Thanos
Mar 12, 2003·Genes & Development·Tiaojiang XiaoBrian D Strahl
Mar 12, 2005·The Journal of Biological Chemistry·Andrew J BannisterTony Kouzarides
Oct 18, 2005·Molecular and Cellular Biology·Bhargavi RaoJason D Lieb
Oct 13, 2006·Molecular and Cellular Biology·Christopher R VakocGerd A Blobel
Nov 8, 2006·Molecular and Cellular Biology·Tiaojiang XiaoBrian D Strahl
Aug 19, 2007·Oncogene·A VaqueroD Reinberg
Sep 19, 2008·Genome Biology·Yong ZhangX Shirley Liu
Jun 16, 2010·The Journal of Biological Chemistry·Arunkumar DhayalanAlbert Jeltsch
Sep 4, 2010·Cell·Jung-Shin LeeAli Shilatifard
Jan 18, 2011·The Journal of Biological Chemistry·Wen YuanBing Zhu
May 10, 2011·Molecular Cell·Frank W SchmitgesNicolas H Thomä
Aug 30, 2011·Current Opinion in Structural Biology·Patrick M LombardiDavid W Christianson
Jan 24, 2012·Nature Reviews. Molecular Cell Biology·Eric J Wagner, Phillip B Carpenter
Mar 30, 2012·Omics : a Journal of Integrative Biology·Guangchuang YuQing-Yu He
Apr 21, 2012·Briefings in Bioinformatics·Helga ThorvaldsdóttirJill P Mesirov
Oct 30, 2012·Bioinformatics·Alexander DobinThomas R Gingeras
Jan 18, 2013·PloS One·Colin T MaguireMaureen L Condic
Mar 12, 2013·Molecular Cell·Eliezer Calo, Joanna Wysocka
May 3, 2013·The New England Journal of Medicine·UNKNOWN Cancer Genome Atlas Research NetworkGreg Eley
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Jan 3, 2014·The Journal of Clinical Investigation·Alison C West, Ricky W Johnstone
Apr 3, 2014·Cold Spring Harbor Perspectives in Biology·Edward Seto, Minoru Yoshida
Apr 29, 2014·Pharmacology & Therapeutics·Prithviraj BoseSteven Grant
May 7, 2014·Nucleic Acids Research·Fidel RamírezThomas Manke
Sep 10, 2014·Current Protocols in Bioinformatics·Aaron R Quinlan
Jan 22, 2015·Nucleic Acids Research·Matthew E RitchieGordon K Smyth

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Software Mentioned

R package ChIPseeker
findMotifsGenome
IGV
clusterProfiler
Integrative Genomics Viewer ( IGV
edgeR
Integrative Genomics Viewer ( IGV )
ggplot2
BEDtools
limma

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