SCML2 Establishes the Male Germline Epigenome through Regulation of Histone H2A Ubiquitination

被引:117
作者
Hasegawa, Kazuteru [1 ,4 ]
Sin, Ho-Su [1 ,4 ]
Maezawa, So [1 ,4 ]
Broering, Tyler J. [1 ,4 ]
Kartashov, Andrey V. [2 ,4 ]
Alavattam, Kris G. [1 ,4 ]
Ichijima, Yosuke [1 ,4 ]
Zhang, Fan [3 ,4 ]
Bacon, W. Clark [2 ,4 ]
Greis, Kenneth D. [5 ]
Andreassen, Paul R. [3 ,4 ]
Barski, Artem [2 ,4 ]
Namekawa, Satoshi H. [1 ,4 ]
机构
[1] Cincinnati Childrens Hosp Med Ctr, Div Reprod Sci, Div Dev Biol, Perinatal Inst, Cincinnati, OH 45229 USA
[2] Cincinnati Childrens Hosp Med Ctr, Div Allergy & Immunol, Div Human Genet, Cincinnati, OH 45229 USA
[3] Cincinnati Childrens Hosp Med Ctr, Div Expt Hematol & Canc Biol, Cincinnati, OH 45229 USA
[4] Univ Cincinnati, Coll Med, Dept Pediat, Cincinnati, OH 45229 USA
[5] Univ Cincinnati, Coll Med, Dept Canc Biol, Cincinnati, OH 45229 USA
基金
日本学术振兴会;
关键词
POSTMEIOTIC SEX-CHROMATIN; DNA-DAMAGE RESPONSE; MOUSE X-CHROMOSOME; STEM-CELLS; POLYCOMB COMPLEXES; GENE-EXPRESSION; DIFFERENTIATION; UBIQUITYLATION; TRANSCRIPTOME; TESTIS;
D O I
10.1016/j.devcel.2015.01.014
中图分类号
Q2 [细胞生物学];
学科分类号
071013 [干细胞生物学];
摘要
Gametogenesis is dependent on the expression of germline-specific genes. However, it remains unknown how the germline epigenome is distinctly established from that of somatic lineages. Here we show that genes commonly expressed in somatic lineages and spermatogenesis-progenitor cells undergo repression in a genome-wide manner in late stages of the male germline and identify underlying mechanisms. SCML2, a germline-specific subunit of a Polycomb repressive complex 1 (PRC1), establishes the unique epigenome of the male germline through two distinct antithetical mechanisms. SCML2 works with PRC1 and promotes RNF2-dependent ubiquitination of H2A, thereby marking somatic/progenitor genes on autosomes for repression. Paradoxically, SCML2 also prevents RNF2-dependent ubiquitination of H2A on sex chromosomes during meiosis, thereby enabling unique epigenetic programming of sex chromosomes for male reproduction. Our results reveal divergent mechanisms involving a shared regulator by which the male germline epigenome is distinguished from that of the soma and progenitor cells.
引用
收藏
页码:574 / 588
页数:15
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