SCML2 Establishes the Male Germline Epigenome through Regulation of Histone H2A Ubiquitination
Copyright policy )SCML2 Establishes the Male Germline Epigenome through Regulation of Histone H2A Ubiquitination
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.
- University of Cincinnati United States
- University System of Ohio United States
- University of California, San Francisco United States
- Cincinnati Children's Hospital Medical Center United States
- University of Cincinnati Medical Center United States
Epigenomics, Male, Chromosomal Proteins, Non-Histone, Messenger, Cell Cycle Proteins, Medical and Health Sciences, Histones, Immunoenzyme Techniques, Mice, Testis, Developmental, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Polycomb Repressive Complex 1, Cultured, Sex Chromosomes, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Gene Expression Regulation, Developmental, Biological Sciences, Chromosomal Proteins, Meiosis, Stem Cell Research - Nonembryonic - Non-Human, Female, Western, Biotechnology, Chromatin Immunoprecipitation, 1.1 Normal biological development and functioning, Cells, Knockout, Ubiquitin-Protein Ligases, Blotting, Western, Real-Time Polymerase Chain Reaction, Underpinning research, Genetics, Animals, Gene Silencing, Spermatogenesis, Adaptor Proteins, Signal Transducing, Ubiquitin, Contraception/Reproduction, Gene Expression Profiling, Human Genome, Signal Transducing, Ubiquitination, Non-Histone, Stem Cell Research, Repressor Proteins, Germ Cells, Gene Expression Regulation, RNA, Biomarkers, Developmental Biology
Epigenomics, Male, Chromosomal Proteins, Non-Histone, Messenger, Cell Cycle Proteins, Medical and Health Sciences, Histones, Immunoenzyme Techniques, Mice, Testis, Developmental, Cells, Cultured, Oligonucleotide Array Sequence Analysis, Polycomb Repressive Complex 1, Cultured, Sex Chromosomes, Blotting, Reverse Transcriptase Polymerase Chain Reaction, Intracellular Signaling Peptides and Proteins, Adaptor Proteins, Gene Expression Regulation, Developmental, Biological Sciences, Chromosomal Proteins, Meiosis, Stem Cell Research - Nonembryonic - Non-Human, Female, Western, Biotechnology, Chromatin Immunoprecipitation, 1.1 Normal biological development and functioning, Cells, Knockout, Ubiquitin-Protein Ligases, Blotting, Western, Real-Time Polymerase Chain Reaction, Underpinning research, Genetics, Animals, Gene Silencing, Spermatogenesis, Adaptor Proteins, Signal Transducing, Ubiquitin, Contraception/Reproduction, Gene Expression Profiling, Human Genome, Signal Transducing, Ubiquitination, Non-Histone, Stem Cell Research, Repressor Proteins, Germ Cells, Gene Expression Regulation, RNA, Biomarkers, Developmental Biology
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