Cited by 89Epigenetics and DNA MethylationPluripotent Stem Cells ResearchGenetic Syndromes and Imprinting

DNA Methylation Is Required for Silencing of Ant4 , an Adenine Nucleotide Translocase Selectively Expressed in Mouse Embryonic Stem Cells and Germ Cells

Rodić, Nemanja, Oka, Masahiro, Hamazaki, Takashi, Murawski, Matthew R., Jorgensen, Marda, Maatouk, Danielle M., Resnick, James L., Li, En +1 more·2005·STEM CELLS

Abstract

The capacity for cellular differentiation is governed not only by the repertoire of available transcription factors but by the accessibility of cis-regulatory elements. Studying changes in epigenetic modifications during stem cell differentiation will help us understand how cells maintain or lose differentiation potential. We investigated changes in DNA methylation during the transition of pluripotent embryonic stem cells (ESCs) into differentiated cell types. Using a methylation-sensitive restriction fingerprinting method, we identified a novel adenine nucleotide (ADP/ATP) translocase gene, Ant4, that was selectively hypomethylated and expressed in undifferentiated mouse ESCs. In contrast to other pluripotent stem cell-specific genes such as Oct-4 and Nanog, the Ant4 gene was readily derepressed in differentiated cells after 5-aza-2'-deoxycytidine treatment. Moreover, expression of de novo DNA methyltransferases Dnmt3a and Dnmt3b was essential for repression and DNA methylation of the Ant4 gene during ESC differentiation. Although the deduced amino acid sequence of Ant4 is highly homologous to the previously identified Ant isoforms, the expression of Ant4 was uniquely restricted to developing gametes in adult mice, and its promoter hypomethylation was observed only in testis. Additionally, Ant4 was expressed in primordial germ cells. These data indicate that Ant4 is a pluripotent stem cell- and germ cell-specific isoform of adenine nucleotide translocase in mouse and that DNA methylation plays a primary role in its transcriptional silencing in somatic cells.

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Crossref · 10.1634/stemcells.2005-0119

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Authors
Rodić, N., Oka, M., Hamazaki, T., Murawski, M. R., Jorgensen, M., Maatouk, D. M., Resnick, J. L., Li, E., & Terada, N.
Affiliations
  • University of Florida Health (US)
  • Harvard University (US)
Venue
STEM CELLS
Published
2005-10
Volume
23
Issue
9
Pages
1314-1323
ISSN
  • 1066-5099 (ISSN-L)
  • 1549-4918
OpenAlex
W1966377847
Cited by
89
References
46
Citations by year
2026: 1 · 2024: 2 · 2023: 3 · 2022: 1 · 2021: 4 · 2020: 3 · 2019: 3 · 2018: 2 · 2017: 1 · 2016: 3 · 2015: 2 · 2014: 3 · 2013: 5 · 2012: 3
FWCI
3.26
Type
journal article
Language
en
Open access
closed
Locations
  • Stem Cells (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health
  • National Institute of Diabetes and Digestive and Kidney Diseases (DK 59699, R01DK059699)
  • National Center for Research Resources (R21RR017001, RR 17001)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Pluripotent Stem Cells Research
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
adenine nucleotide translocase, DNA methylation, transcriptional silencing, mouse embryonic stem cells, stem cell differentiation, germ cells, primordial germ cells, de novo DNA methyltransferases, DNMT3A, DNMT3B, decitabine, testis, pluripotency, cis-regulatory elements
MeSH terms
DNA Methyltransferase 3A, DNA Methyltransferase 3B, Mitochondrial ADP, ATP Translocases, Animals, Base Sequence, Cell Differentiation, DNA (Cytosine-5-)-Methyltransferases, Embryo, Mammalian, Gene Expression Regulation, Male, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger, Spermatozoa, Stem Cells, Testis, DNA Methylation, Gene Silencing, Mice

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