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Open Access Highly Accessed Research article

Transcriptional repression and DNA hypermethylation of a small set of ES cell marker genes in male germline stem cells

Masanori Imamura1, Kyoko Miura1, Kumiko Iwabuchi1, Tomoko Ichisaka1, Masato Nakagawa1, Jiyoung Lee2, Mito Kanatsu-Shinohara23, Takashi Shinohara2 and Shinya Yamanaka14*

Author Affiliations

1 Department of Stem Cell Biology, Institute for Frontier Medical Sciences, Kyoto University, Kyoto 606-8507, Japan

2 Department of Molecular Genetics, Graduate School of Medicine, Kyoto University, Kyoto 606-8507, Japan

3 Horizontal Medical Research Organization, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan

4 CREST, Japan Science and Technology Agency, Saitama, Japan

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BMC Developmental Biology 2006, 6:34  doi:10.1186/1471-213X-6-34

Published: 21 July 2006

Abstract

Background

We previously identified a set of genes called ECATs (ES cell-associated transcripts) that are expressed at high levels in mouse ES cells. Here, we examine the expression and DNA methylation of ECATs in somatic cells and germ cells.

Results

In all ECATs examined, the promoter region had low methylation levels in ES cells, but higher levels in somatic cells. In contrast, in spite of their lack of pluripotency, male germline stem (GS) cells expressed most ECATs and exhibited hypomethylation of ECAT promoter regions. We observed a similar hypomethylation of ECAT loci in adult testis and isolated sperm. Some ECATs were even less methylated in male germ cells than in ES cells. However, a few ECATs were not expressed in GS cells, and most of them targets of Oct3/4 and Sox2. The Octamer/Sox regulatory elements were hypermethylated in these genes. In addition, we found that GS cells express little Sox2 protein and low Oct3/4 protein despite abundant expression of their transcripts.

Conclusion

Our results suggest that DNA hypermethylation and transcriptional repression of a small set of ECATs, together with post-transcriptional repression of Oct3/4 and Sox2, contribute to the loss of pluripotency in male germ cells.