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BOR - Papers in Press, published online ahead of print January 9, 2008.
Biol Reprod 2008, 10.1095/biolreprod.107.066522
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BIOLOGY OF REPRODUCTION 78, 816–821 (2008)
DOI: 10.1095/biolreprod.107.066522
© 2008 by the Society for the Study of Reproduction, Inc.

Gamete Biology; 

DNA Hypomethylation Circuit of the Mouse Oocyte-Specific Histone H1foo Gene in Female Germ Cell Lineage1

Chiaki Maeda , Shun Sato , Naoko Hattori , Satoshi Tanaka , Shintaro Yagi , and Kunio Shiota 2

Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan

ABSTRACT

The oocyte-specific subtype of the linker histone H1 is H1FOO, which constitutes a major part of oocyte chromatin. H1foo is expressed in growing oocytes, through fertilization, up until the two–cell embryo stage, when it is subsequently replaced by somatic H1 subtypes. To elucidate whether an epigenetic mechanism is involved in the limited expression of H1foo, we analyzed the dynamics of the DNA methylation status of the H1foo locus in germ and somatic cells. We identified a tissue-dependent and differentially methylated region (T-DMR) upstream of the H1foo gene, which was hypermethylated in sperm, somatic cells, and stem cell lines. This region was specifically unmethylated in the ovulated oocyte, where H1foo is expressed. 5-Aza-2'-deoxycytidine treatments and luciferase assays provided in vitro evidence that DNA methylation plays a role in repressing H1foo in nonexpressing cells. DNA methylation analyses of fetal germ cells revealed the T-DMR to be hypomethylated in female and male germ cells at Embryonic Day 9.5 (E9.5), whereas it was highly methylated in somatic cells at this stage. Intriguingly, the unmethylated status was continuously observed throughout oogenesis at E9.5, E12.5, E15.5, E18.5, in mature oocytes, and after fertilization, in E3.5 blastocysts. In comparison, male germ cells acquired methylation beyond E18.5. These data demonstrate a continuously unmethylated circuit at the H1foo locus in the female germline.

DNA methylation, epigenetics, gametogenesis, gene regulation, histone H1, oocyte, oocyte development

FOOTNOTES

1Supported by the Program for Promotion of Basic Research Activities for Innovative Biosciences and the Grant-in-aid for Scientific Research, Ministry of Education, Culture, Sports, Science and Technology, Japan (15080202) to K.S.

Correspondence: 2Kunio Shiota, Laboratory of Cellular Biochemistry, Animal Resource Sciences/Veterinary Medical Sciences, The University of Tokyo, Bunkyo-ku, Tokyo 113-8657, Japan. FAX: 81 3 5841 8189; e-mail: ashiota{at}mail.ecc.u-tokyo.ac.jp






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