Implication of DNA demethylation and bivalent histone modification for selective gene regulation in mouse primordial germ cells

PloS One
Kentaro MochizukiYasuhisa Matsui

Abstract

Primordial germ cells (PGCs) sequentially induce specific genes required for their development. We focused on epigenetic changes that regulate PGC-specific gene expression. mil-1, Blimp1, and Stella are preferentially expressed in PGCs, and their expression is upregulated during PGC differentiation. Here, we first determined DNA methylation status of mil-1, Blimp1, and Stella regulatory regions in epiblast and in PGCs, and found that they were hypomethylated in differentiating PGCs after E9.0, in which those genes were highly expressed. We used siRNA to inhibit a maintenance DNA methyltransferase, Dnmt1, in embryonic stem (ES) cells and found that the flanking regions of all three genes became hypomethylated and that expression of each gene increased 1.5- to 3-fold. In addition, we also found 1.5- to 5-fold increase of the PGC genes in the PGCLCs (PGC-like cells) induced form ES cells by knockdown of Dnmt1. We also obtained evidence showing that methylation of the regulatory region of mil-1 resulted in 2.5-fold decrease in expression in a reporter assay. Together, these results suggested that DNA demethylation does not play a major role on initial activation of the PGC genes in the nascent PGCs but contributed to enhancement of...Continue Reading

References

Jan 1, 1983·Annals of the New York Academy of Sciences·R N Taylor, K M Fulford
Jul 9, 1996·Proceedings of the National Academy of Sciences of the United States of America·C De SmetT Boon
May 20, 1998·Biochemical and Biophysical Research Communications·J Seligman, D C Page
Jan 26, 2000·Development, Growth & Differentiation·T YoshimizuY Matsui
Feb 17, 2000·Nature·W MayerThomas Haaf
May 10, 2000·Current Biology : CB·J OswaldJ Walter
Nov 13, 2001·Developmental Cell·G FuhrmannA J Cooney
Jul 19, 2002·Nature·Mitinori SaitouM Azim Surani
Sep 3, 2002·Mechanisms of Development·Petra HajkovaM Azim Surani
Sep 7, 2002·International Journal of Cancer. Journal International Du Cancer·Ali O GüreYao-Tseng Chen
Aug 30, 2003·Science·Masayuki TsudaYumiko Saga
Jul 16, 2004·Developmental Dynamics : an Official Publication of the American Association of Anatomists·Satomi S TanakaYasuhisa Matsui
Sep 3, 2004·Cancer Research·Michael KoslowskiOzlem Türeci
Oct 16, 2004·EMBO Reports·James KehlerAlexey Tomilin
Jun 7, 2005·Current Biology : CB·Michael PohlersChristian Hagemeier
Jun 7, 2005·Nature·Yasuhide OhinataM Azim Surani
Jul 22, 2005·Nature Reviews. Cancer·Andrew J G SimpsonLloyd J Old
Oct 21, 2005·The Journal of Biological Chemistry·Jörg StorreStefan Gaubatz
Dec 14, 2005·Biochemical and Biophysical Research Communications·Steven Shoei-Lung LiSher Singh
Jan 27, 2006·Genesis : the Journal of Genetics and Development·Bernhard PayerM Azim Surani
May 4, 2006·International Journal of Cancer. Journal International Du Cancer·Rintaro MikataHiromitsu Saisho
Jun 7, 2007·Genesis : the Journal of Genetics and Development·Teresa GallardoDiego H Castrillon
Oct 30, 2007·Epigenetics : Official Journal of the DNA Methylation Society·Maja Klug, Michael Rehli
Dec 22, 2007·Nature·Ian ChambersAustin Smith
Jan 17, 2008·Nature Reviews. Genetics·Hiroyuki Sasaki, Yasuhisa Matsui
Feb 19, 2008·Genes & Development·Atsushi Suzuki, Yumiko Saga
Apr 9, 2008·Developmental Biology·Daiji OkamuraYasuhisa Matsui
Jun 28, 2008·Reproduction : the Official Journal of the Society for the Study of Fertility·Yasuhide OhinataMitinori Saitou
Jul 16, 2008·Nature Genetics·Masashi YamajiMitinori Saitou
Aug 1, 2008·Biology of Reproduction·Sarah M KehoeNaohiro Terada

Citations

Sep 18, 2013·Proceedings of the National Academy of Sciences of the United States of America·Bluma J LeschD C Page
Nov 25, 2015·Seminars in Cell & Developmental Biology·Kirsten Hogg, Patrick Western
Jul 23, 2013·Molecular Reproduction and Development·Yasuhisa Matsui, Kentaro Mochizuki
Sep 3, 2013·Molecular Reproduction and Development·Masanori ImamuraHideyuki Okano
Jun 6, 2015·Cellular and Molecular Life Sciences : CMLS·Valérie J RobertFrancesca Palladino
Jun 18, 2016·Seminars in Immunopathology·Undraga SchagdarsurenginAndreas Meinhardt
Sep 1, 2016·Nature Reviews. Urology·Undraga Schagdarsurengin, Klaus Steger
Sep 22, 2016·Parasitology Research·Mengmeng TianChangliang Zhu
Mar 20, 2018·Animal : an International Journal of Animal Bioscience·M McGowanG Boe-Hansen
Jul 10, 2018·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Hitoshi InadaNoriko Osumi
Dec 14, 2018·Genes·Marthe LaisnéPierre-Antoine Defossez
Feb 27, 2015·Biology of Reproduction·Fanhui ZengHu Wang
Nov 26, 2020·Nature Communications·Christopher B MulhollandHeinrich Leonhardt
Sep 25, 2014·Development·Bluma J Lesch, D C Page

Methods Mentioned

BETA
transgenic
PCR
ICE
transfection
ChIP
ICEs
Assay
transfections
Immunoprecipitation

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