Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells

DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes
Tomohiko AkiyamaMinoru S H Ko

Abstract

Mouse embryonic stem cells (mESCs) have a remarkable capacity to maintain normal genome stability and karyotype in culture. We previously showed that infrequent bursts of Zscan4 expression (Z4 events) are important for the maintenance of telomere length and genome stability in mESCs. However, the molecular details of Z4 events remain unclear. Here we show that Z4 events involve unexpected transcriptional derepression in heterochromatin regions that usually remain silent. During a Z4 event, we see rapid derepression and rerepression of heterochromatin leading to a burst of transcription that coincides with transient histone hyperacetylation and DNA demethylation, clustering of pericentromeric heterochromatin around the nucleolus, and accumulation of activating and repressive chromatin remodelling complexes. This heterochromatin-based transcriptional activity suggests that mESCs may maintain their extraordinary genome stability at least in part by transiently resetting their heterochromatin.

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Citations

Mar 22, 2016·Stem Cell Reports·Yoko Nakai-Futatsugi, Hitoshi Niwa
Sep 2, 2015·DNA Research : an International Journal for Rapid Publication of Reports on Genes and Genomes·Tomokazu AmanoMinoru S H Ko
May 1, 2016·In Vitro Cellular & Developmental Biology. Animal·Lioudmila V SharovaMinoru S H Ko
Sep 30, 2016·Cell Reports·Mélanie A Eckersley-MaslinWolf Reik
Oct 5, 2016·In Vitro Cellular & Developmental Biology. Animal·Kei-Ichiro IshiguroMinoru S H Ko
Oct 5, 2016·In Vitro Cellular & Developmental Biology. Animal·Kei-Ichiro IshiguroMinoru S H Ko
May 2, 2017·Nature Genetics·Jennifer L WhiddonStephen J Tapscott
Jan 30, 2019·Genes & Development·Mélanie Eckersley-MaslinWolf Reik
Apr 26, 2019·The Journal of Reproduction and Development·Kazuki TakahashiKen Sawai
Jul 16, 2019·Nucleic Acids Research·Weiyu ZhangXinyi Lu
Jan 15, 2020·Nature Cell Biology·Zhenhua HuWee-Wei Tee
May 20, 2020·EMBO Reports·Annaelena TroianoGeppino Falco
Apr 25, 2018·Nature Reviews. Molecular Cell Biology·Melanie A Eckersley-MaslinWolf Reik
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Dec 19, 2017·Chromosoma·Mathieu Tardat, Jérôme Déjardin
Aug 28, 2020·Development·Marion Genet, Maria-Elena Torres-Padilla
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Jul 27, 2021·Frontiers in Cell and Developmental Biology·Clara Lopes Novo
Sep 7, 2021·Emerging Topics in Life Sciences·Fatma Dogan, Nicholas R Forsyth
Jul 2, 2020·Cell Reports·Tomomi OkunoKei Miyamoto

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Methods Mentioned

BETA
PCR
immunoprecipitation
FACS
RNA-seq
Fluorescence
ChIP-seq
gel filtration
acetylation
MeDIP-seq

Software Mentioned

NIH Image
Bowtie

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