Abstract
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.
Copyright © 2015 Elsevier Inc. All rights reserved.
Publication types
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Research Support, N.I.H., Extramural
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing
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Animals
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Biomarkers / metabolism
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Blotting, Western
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Cell Cycle Proteins
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Cells, Cultured
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Chromatin Immunoprecipitation
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Chromosomal Proteins, Non-Histone
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Epigenomics*
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Female
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Gene Expression Profiling
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Gene Expression Regulation, Developmental*
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Gene Silencing
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Germ Cells
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Histones / metabolism*
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Immunoenzyme Techniques
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Intracellular Signaling Peptides and Proteins / physiology
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Male
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Meiosis / genetics
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Mice
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Mice, Knockout
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Oligonucleotide Array Sequence Analysis
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Polycomb Repressive Complex 1 / genetics
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Polycomb Repressive Complex 1 / metabolism*
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Polycomb Repressive Complex 1 / physiology
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RNA, Messenger / genetics
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Real-Time Polymerase Chain Reaction
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Repressor Proteins / physiology
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Reverse Transcriptase Polymerase Chain Reaction
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Sex Chromosomes / genetics
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Spermatogenesis
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Testis / cytology
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Testis / metabolism*
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Ubiquitin / metabolism*
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Ubiquitin-Protein Ligases / physiology
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Ubiquitination
Substances
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Adaptor Proteins, Signal Transducing
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Biomarkers
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Cell Cycle Proteins
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Chromosomal Proteins, Non-Histone
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Dppa3 protein, mouse
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Histones
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Intracellular Signaling Peptides and Proteins
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MDC1 protein, mouse
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RNA, Messenger
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Repressor Proteins
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Ubiquitin
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Polycomb Repressive Complex 1
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Rnf2 protein, mouse
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Ubiquitin-Protein Ligases