Lysine 4 of histone H3.3 is required for embryonic stem cell differentiation, histone enrichment at regulatory regions and transcription accuracy.

Nature Genetics
Maja GehreKyung-Min Noh

Abstract

Mutations in enzymes that modify histone H3 at lysine 4 (H3K4) or lysine 36 (H3K36) have been linked to human disease, yet the role of these residues in mammals is unclear. We mutated K4 or K36 to alanine in the histone variant H3.3 and showed that the K4A mutation in mouse embryonic stem cells (ESCs) impaired differentiation and induced widespread gene expression changes. K4A resulted in substantial H3.3 depletion, especially at ESC promoters; it was accompanied by reduced remodeler binding and increased RNA polymerase II (Pol II) activity. Regulatory regions depleted of H3.3K4A showed histone modification alterations and changes in enhancer activity that correlated with gene expression. In contrast, the K36A mutation did not alter H3.3 deposition and affected gene expression at the later stages of differentiation. Thus, H3K4 is required for nucleosome deposition, histone turnover and chromatin remodeler binding at regulatory regions, where tight regulation of Pol II activity is necessary for proper ESC differentiation.

References

Apr 2, 2003·Circulation·Tomosaburo TakahashiRichard T Lee
Feb 27, 2007·Cell·Bing LiJerry L Workman
Jul 3, 2007·Nature·Tarjei S MikkelsenBradley E Bernstein
Feb 6, 2010·Science·Reini F LucoTom Misteli
Feb 16, 2010·Current Opinion in Genetics & Development·Simon J ElsaesserC David Allis
Jul 24, 2010·Proceedings of the National Academy of Sciences of the United States of America·Peter W LewisC David Allis
Dec 16, 2011·Nucleic Acids Research·Pablo Perez-PineraCharles A Gersbach
Jan 24, 2012·Nature Reviews. Molecular Cell Biology·Eric J Wagner, Phillip B Carpenter
Jan 31, 2012·Nature Genetics·Gang WuUNKNOWN St. Jude Children's Research Hospital–Washington University Pediatric Cancer Genome Project
Mar 6, 2012·Nature Methods·Ben Langmead, Steven L Salzberg
Jun 23, 2012·Genome Research·Simon AndersWolfgang Huber
Jun 26, 2012·Nucleic Acids Research·Andreas UntergasserSteven G Rozen
Jun 30, 2012·Nature Methods·Johannes SchindelinAlbert Cardona
Nov 13, 2012·Current Biology : CB·Martina Hödl, Konrad Basler
Oct 26, 2013·Nature Protocols·F Ann RanFeng Zhang
Apr 4, 2014·Bioinformatics·Anthony M BolgerBjoern Usadel
Oct 15, 2014·Cell Reports·Thomas ConradUlf Andersson Orom
Jul 15, 2015·Genes & Development·Chuan-Wei JangTerry Magnuson
Jan 28, 2016·Nature·Maud de DieuleveultMatthieu Gérard
Apr 16, 2016·Nucleic Acids Research·Fidel RamírezThomas Manke
Apr 24, 2016·Nucleic Acids Research·Yang WangChunyan Zhou

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Citations

Jul 16, 2020·Nature Reviews. Molecular Cell Biology·Sara Martire, Laura A Banaszynski
Oct 15, 2020·Open Biology·Amanuel Tafessu, Laura A Banaszynski
Aug 29, 2020·Annual Review of Genetics·Benjamin Loppin, Frédéric Berger
Jan 10, 2021·International Journal of Molecular Sciences·Kateryna FalCristel C Carles
Feb 20, 2021·Stem Cells International·Zi Hao ZhengYuin-Han Loh
May 8, 2021·Frontiers in Cell and Developmental Biology·Reuben FranklinSihem Cheloufi
Jul 3, 2021·International Journal of Molecular Sciences·Olivia Morrison, Jitendra Thakur
Mar 31, 2021·Annual Review of Genomics and Human Genetics·Paul B Talbert, Steven Henikoff

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Methods Mentioned

BETA
RNA-seq
immunoprecipitation
PCR
pulldown
Hi-C
PRO-seq
dissection
genotyping
electrophoresis
ChIP

Software Mentioned

Ensembl BioMart
Bowtie2
R
plot
Bioconductor
DiffBind
pheatmap
MACS2
ngs
LiftOver

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