Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline

So Maezawa, Kazuteru Hasegawa, Masashi Yukawa, Naoki Kubo, Akihiko Sakashita, Kris G. Alavattam, Ho Su Sin, Andrey V. Kartashov, Hiroyuki Sasaki, Artem Barski, Satoshi H. Namekawa

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Abstract

Repressive H3K27me3 and active H3K4me2/3 together form bivalent chromatin domains, molecular hallmarks of developmental potential. In the male germline, these domains are thought to persist into sperm to establish totipotency in the next generation. However, it remains unknown how H3K27me3 is established on specific targets in the male germline. Here, we demonstrate that a germline-specific Polycomb protein, SCML2, binds to H3K4me2/3-rich hypomethylated promoters in undifferentiated spermatogonia to facilitate H3K27me3. Thus, SCML2 establishes bivalent domains in the male germline of mice. SCML2 regulates two major classes of bivalent domains: Class I domains are established on developmental regulator genes that are silent throughout spermatogenesis, while class II domains are established on somatic genes silenced during late spermatogenesis. We propose that SCML2-dependent H3K27me3 in the male germline prepares the expression of developmental regulator and somatic genes in embryonic development.

Original languageEnglish
Pages (from-to)4957-4962
Number of pages6
JournalProceedings of the National Academy of Sciences of the United States of America
Volume115
Issue number19
DOIs
Publication statusPublished - May 8 2018

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Developmental Genes
Spermatogenesis
Regulator Genes
Proteins
Spermatogonia
Chromatin
Embryonic Development
Spermatozoa
Genes

All Science Journal Classification (ASJC) codes

  • General

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Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline. / Maezawa, So; Hasegawa, Kazuteru; Yukawa, Masashi; Kubo, Naoki; Sakashita, Akihiko; Alavattam, Kris G.; Sin, Ho Su; Kartashov, Andrey V.; Sasaki, Hiroyuki; Barski, Artem; Namekawa, Satoshi H.

In: Proceedings of the National Academy of Sciences of the United States of America, Vol. 115, No. 19, 08.05.2018, p. 4957-4962.

Research output: Contribution to journalArticle

Maezawa, S, Hasegawa, K, Yukawa, M, Kubo, N, Sakashita, A, Alavattam, KG, Sin, HS, Kartashov, AV, Sasaki, H, Barski, A & Namekawa, SH 2018, 'Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline', Proceedings of the National Academy of Sciences of the United States of America, vol. 115, no. 19, pp. 4957-4962. https://doi.org/10.1073/pnas.1804512115
Maezawa, So ; Hasegawa, Kazuteru ; Yukawa, Masashi ; Kubo, Naoki ; Sakashita, Akihiko ; Alavattam, Kris G. ; Sin, Ho Su ; Kartashov, Andrey V. ; Sasaki, Hiroyuki ; Barski, Artem ; Namekawa, Satoshi H. / Polycomb protein SCML2 facilitates H3K27me3 to establish bivalent domains in the male germline. In: Proceedings of the National Academy of Sciences of the United States of America. 2018 ; Vol. 115, No. 19. pp. 4957-4962.
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