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

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 mo...

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Published in:	DNA research Vol. 22; no. 5; pp. 307 - 318
Main Authors:	Akiyama, Tomohiko, Xin, Li, Oda, Mayumi, Sharov, Alexei A., Amano, Misa, Piao, Yulan, Cadet, J. Scotty, Dudekula, Dawood B., Qian, Yong, Wang, Weidong, Ko, Shigeru B. H., Ko, Minoru S. H.
Format:	Journal Article
Language:	English
Published:	England Oxford University Press 01.10.2015
Subjects:	Acetylation Animals Cell Nucleolus - metabolism Chromatin Assembly and Disassembly DNA Methylation Epigenesis, Genetic Genomic Instability Heterochromatin - genetics Histones - metabolism Mice Mouse Embryonic Stem Cells - metabolism Telomere Homeostasis - genetics Transcription Factors - genetics Transcription Factors - physiology Transcription, Genetic pericentromere embryonic stem cells heterochromatin
ISSN:	1340-2838, 1756-1663, 1756-1663
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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.
AbstractList	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.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. 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.
Author	Piao, Yulan Amano, Misa Cadet, J. Scotty Ko, Shigeru B. H. Ko, Minoru S. H. Wang, Weidong Qian, Yong Dudekula, Dawood B. Akiyama, Tomohiko Xin, Li Oda, Mayumi Sharov, Alexei A.
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Snippet	Mouse embryonic stem cells (mESCs) have a remarkable capacity to maintain normal genome stability and karyotype in culture. We previously showed that...
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SubjectTerms	Acetylation Animals Cell Nucleolus - metabolism Chromatin Assembly and Disassembly DNA Methylation Epigenesis, Genetic Genomic Instability Heterochromatin - genetics Histones - metabolism Mice Mouse Embryonic Stem Cells - metabolism Telomere Homeostasis - genetics Transcription Factors - genetics Transcription Factors - physiology Transcription, Genetic
Title	Transient bursts of Zscan4 expression are accompanied by the rapid derepression of heterochromatin in mouse embryonic stem cells
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