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 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.
Department of Systems Medicine, Keio University School of Medicine, Tokyo 160, Japan Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Tomohiko
T
Akiyama
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Li
L
Xin
Department of Systems Medicine, Keio University School of Medicine, Tokyo 160, Japan.
Mayumi
M
Oda
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Alexei A
AA
Sharov
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Misa
M
Amano
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Yulan
Y
Piao
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
J Scotty
JS
Cadet
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Dawood B
DB
Dudekula
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Yong
Y
Qian
Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA.
Weidong
W
Wang
Department of Systems Medicine, Keio University School of Medicine, Tokyo 160, Japan.
Shigeru B H
SB
Ko
Department of Systems Medicine, Keio University School of Medicine, Tokyo 160, Japan Laboratory of Genetics, National Institute on Aging, NIH, Baltimore, MD 21224, USA ko.minoru@keio.jp.
Minoru S H
MS
Ko
D000107:Acetylation; D000818:Animals; D002466:Cell Nucleolus / Q000378:metabolism; D042002:Chromatin Assembly and Disassembly; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D042822:Genomic Instability; D006570:Heterochromatin / Q000235:genetics*; D006657:Histones / Q000378:metabolism; D051379:Mice; D000066450:Mouse Embryonic Stem Cells / Q000378:metabolism*; D059505:Telomere Homeostasis / Q000235:genetics*; D014157:Transcription Factors / Q000235:genetics* / Q000502:physiology; D014158:Transcription, Genetic
D006570:Heterochromatin; D006657:Histones; D014157:Transcription Factors; C000588925:Zscan4c protein, mouse
embryonic stem cells; heterochromatin; pericentromere