Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse

Yuzuru Kato, Masahiro Kaneda, Kenichiro Hata, Kenji Kumaki, Mizue Hisano, Yuji Kohara, Masaki Okano, En Li, Masami Nozaki, Hiroyuki Sasaki

Research output: Contribution to journalArticle

331 Citations (Scopus)

Abstract

DNA methylation is an important epigenetic modification regulating various biological phenomena, including genomic imprinting and transposon silencing. It is known that methylation of the differentially methylated regions (DMRs) associated with paternally imprinted genes and of some repetitive elements occurs during male germ cell development in the mouse. We have performed a detailed methylation analysis of the paternally methylated DMRs (H19, Dlk1/Gtl2 and Rasgrf1), interspersed repeats [SineB1, intracisternal A particle (IAP) and Line1] and satellite repeats (major and minor) to determine the timing of this de novo methylation in male germ cells. Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process. We found that methylation of all DMRs and repeats occurred progressively in fetal prospermatogonia and was completed by the newborn stage. Analysis of newborn prospermatogonia from germline-specific Dnmt3a and Dnmt3b knockout mice revealed that Dnmt3a mainly methylates the H19 and Dlk1/Gtl2 DMRs and a short interspersed repeat SineB1. Both Dnmt3a and Dnmt3b were involved in the methylation of Rasgrf1 DMR and long interspersed repeats IAP and Line1. Only Dnmt3b was required for the methylation of the satellite repeats. These results indicate both common and differential target specificities of Dnmt3a and Dnmt3b in vivo. Finally, all these sequences showed moderate to severe hypomethylation in Dnmt3L-deficient prospermatogonia, indicating the critical function and broad specificity of this factor in de novo methylation.

Original languageEnglish
Pages (from-to)2272-2280
Number of pages9
JournalHuman Molecular Genetics
Volume16
Issue number19
DOIs
Publication statusPublished - Oct 1 2007
Externally publishedYes

Fingerprint

Nucleic Acid Repetitive Sequences
Germ Cells
Methylation
ras-GRF1
Genomic Imprinting
Biological Phenomena
Methyltransferases
DNA Methylation
Epigenomics
Knockout Mice
Genes
Proteins

All Science Journal Classification (ASJC) codes

  • Molecular Biology
  • Genetics
  • Genetics(clinical)

Cite this

Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. / Kato, Yuzuru; Kaneda, Masahiro; Hata, Kenichiro; Kumaki, Kenji; Hisano, Mizue; Kohara, Yuji; Okano, Masaki; Li, En; Nozaki, Masami; Sasaki, Hiroyuki.

In: Human Molecular Genetics, Vol. 16, No. 19, 01.10.2007, p. 2272-2280.

Research output: Contribution to journalArticle

Kato, Yuzuru ; Kaneda, Masahiro ; Hata, Kenichiro ; Kumaki, Kenji ; Hisano, Mizue ; Kohara, Yuji ; Okano, Masaki ; Li, En ; Nozaki, Masami ; Sasaki, Hiroyuki. / Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. In: Human Molecular Genetics. 2007 ; Vol. 16, No. 19. pp. 2272-2280.
@article{390c994a52f54b6888ba98b8f7fe5bbc,
title = "Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse",
abstract = "DNA methylation is an important epigenetic modification regulating various biological phenomena, including genomic imprinting and transposon silencing. It is known that methylation of the differentially methylated regions (DMRs) associated with paternally imprinted genes and of some repetitive elements occurs during male germ cell development in the mouse. We have performed a detailed methylation analysis of the paternally methylated DMRs (H19, Dlk1/Gtl2 and Rasgrf1), interspersed repeats [SineB1, intracisternal A particle (IAP) and Line1] and satellite repeats (major and minor) to determine the timing of this de novo methylation in male germ cells. Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process. We found that methylation of all DMRs and repeats occurred progressively in fetal prospermatogonia and was completed by the newborn stage. Analysis of newborn prospermatogonia from germline-specific Dnmt3a and Dnmt3b knockout mice revealed that Dnmt3a mainly methylates the H19 and Dlk1/Gtl2 DMRs and a short interspersed repeat SineB1. Both Dnmt3a and Dnmt3b were involved in the methylation of Rasgrf1 DMR and long interspersed repeats IAP and Line1. Only Dnmt3b was required for the methylation of the satellite repeats. These results indicate both common and differential target specificities of Dnmt3a and Dnmt3b in vivo. Finally, all these sequences showed moderate to severe hypomethylation in Dnmt3L-deficient prospermatogonia, indicating the critical function and broad specificity of this factor in de novo methylation.",
author = "Yuzuru Kato and Masahiro Kaneda and Kenichiro Hata and Kenji Kumaki and Mizue Hisano and Yuji Kohara and Masaki Okano and En Li and Masami Nozaki and Hiroyuki Sasaki",
year = "2007",
month = "10",
day = "1",
doi = "10.1093/hmg/ddm179",
language = "English",
volume = "16",
pages = "2272--2280",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "19",

}

TY - JOUR

T1 - Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse

AU - Kato, Yuzuru

AU - Kaneda, Masahiro

AU - Hata, Kenichiro

AU - Kumaki, Kenji

AU - Hisano, Mizue

AU - Kohara, Yuji

AU - Okano, Masaki

AU - Li, En

AU - Nozaki, Masami

AU - Sasaki, Hiroyuki

PY - 2007/10/1

Y1 - 2007/10/1

N2 - DNA methylation is an important epigenetic modification regulating various biological phenomena, including genomic imprinting and transposon silencing. It is known that methylation of the differentially methylated regions (DMRs) associated with paternally imprinted genes and of some repetitive elements occurs during male germ cell development in the mouse. We have performed a detailed methylation analysis of the paternally methylated DMRs (H19, Dlk1/Gtl2 and Rasgrf1), interspersed repeats [SineB1, intracisternal A particle (IAP) and Line1] and satellite repeats (major and minor) to determine the timing of this de novo methylation in male germ cells. Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process. We found that methylation of all DMRs and repeats occurred progressively in fetal prospermatogonia and was completed by the newborn stage. Analysis of newborn prospermatogonia from germline-specific Dnmt3a and Dnmt3b knockout mice revealed that Dnmt3a mainly methylates the H19 and Dlk1/Gtl2 DMRs and a short interspersed repeat SineB1. Both Dnmt3a and Dnmt3b were involved in the methylation of Rasgrf1 DMR and long interspersed repeats IAP and Line1. Only Dnmt3b was required for the methylation of the satellite repeats. These results indicate both common and differential target specificities of Dnmt3a and Dnmt3b in vivo. Finally, all these sequences showed moderate to severe hypomethylation in Dnmt3L-deficient prospermatogonia, indicating the critical function and broad specificity of this factor in de novo methylation.

AB - DNA methylation is an important epigenetic modification regulating various biological phenomena, including genomic imprinting and transposon silencing. It is known that methylation of the differentially methylated regions (DMRs) associated with paternally imprinted genes and of some repetitive elements occurs during male germ cell development in the mouse. We have performed a detailed methylation analysis of the paternally methylated DMRs (H19, Dlk1/Gtl2 and Rasgrf1), interspersed repeats [SineB1, intracisternal A particle (IAP) and Line1] and satellite repeats (major and minor) to determine the timing of this de novo methylation in male germ cells. Furthermore, we have examined the roles of the de novo methyltransferases (Dnmt3a and Dnmt3b) and related protein (Dnmt3L) in this process. We found that methylation of all DMRs and repeats occurred progressively in fetal prospermatogonia and was completed by the newborn stage. Analysis of newborn prospermatogonia from germline-specific Dnmt3a and Dnmt3b knockout mice revealed that Dnmt3a mainly methylates the H19 and Dlk1/Gtl2 DMRs and a short interspersed repeat SineB1. Both Dnmt3a and Dnmt3b were involved in the methylation of Rasgrf1 DMR and long interspersed repeats IAP and Line1. Only Dnmt3b was required for the methylation of the satellite repeats. These results indicate both common and differential target specificities of Dnmt3a and Dnmt3b in vivo. Finally, all these sequences showed moderate to severe hypomethylation in Dnmt3L-deficient prospermatogonia, indicating the critical function and broad specificity of this factor in de novo methylation.

UR - http://www.scopus.com/inward/record.url?scp=34548705374&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548705374&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddm179

DO - 10.1093/hmg/ddm179

M3 - Article

C2 - 17616512

AN - SCOPUS:34548705374

VL - 16

SP - 2272

EP - 2280

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 19

ER -