ArticlePLoS genetics2018
RNF8 and SCML2 cooperate to regulate ubiquitination and H3K27 acetylation for escape gene activation on the sex chromosomes.
Article in PLoS genetics, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 37 papers.
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Who cites it
37 citing papers in PubMed, 62 citations in OpenAlex.
- High-resolution chromatin mapping reveals that CTCF anchors meiotic loops to the chromosome axis.Nature communications · 2026Article
- DAXX directs dual modes of H3.4-to-H3.3 histone replacement in the male germline.Genes & development · 2026Article
- Transcription factor NFYA directs male meiotic entry by regulating accessible chromatin at meiotic promoters in mice.The EMBO journal · 2026Article
- The 3D genome during germline development and meiosis.Trends in genetics : TIG · 2026Review
- Dynamic architecture of mammalian paternal chromatin: histone-to-protamine exchange and post-fertilization reprogramming.Epigenetics & chromatin · 2025Review
- Discordant effects of maternal age on the human MII oocyte transcriptome.Molecular human reproduction · 2025Article
- CTCF-mediated 3D chromatin sets up the gene expression program in the male germline.Nature structural & molecular biology · 2025Article
- KRAB zinc-finger proteins regulate endogenous retroviruses to sculpt germline transcriptomes and genome evolution.Genome research · 2025Article
- Chromatin environment-dependent effects of DOT1L on gene expression in male germ cells.Communications biology · 2025Article
- METTL16 is Required for Meiotic Sex Chromosome Inactivation and DSB Formation and Recombination during Male Meiosis.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Discordant interactions between YAP1 and polycomb group protein SCML2 determine cell fate.iScience · 2023Article
- SCML2 contributes to tumor cell resistance to DNA damage through regulating p53 and CHK1 stability.Cell death and differentiation · 2023Article
- Epigenetic markers in the embryonal germ cell development and spermatogenesis.Basic and clinical andrology · 2023Review
- Sex body: A nest of protein mixture.Frontiers in cell and developmental biology · 2023Review
- Active DNA damage response signaling initiates and maintains meiotic sex chromosome inactivation.Nature communications · 2022Article
- ADAD2 regulates heterochromatin in meiotic and post-meiotic male germ cells via translation of MDC1.Journal of cell science · 2022Article
- Meiotic sex chromosome inactivation and the XY body: a phase separation hypothesis.Cellular and molecular life sciences : CMLS · 2021Review
- Sex Comb on Midleg Like-2 Accelerates Hepatocellular Carcinoma Cell Proliferation and Metastasis by Activating Wnt/β-Catenin/EMT Signaling.Yonsei medical journal · 2021Article
- RNF8 is not required for histone-to-protamine exchange in spermiogenesis†.Biology of reproduction · 2021Article
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Authors and funding
14 authors at 3 institutions in 2 countries.
Funding
Abstract
The sex chromosomes are enriched with germline genes that are activated during the late stages of spermatogenesis. Due to meiotic sex chromosome inactivation (MSCI), these sex chromosome-linked genes must escape silencing for activation in spermatids, thereby ensuring their functions for male reproduction. RNF8, a DNA damage response protein, and SCML2, a germline-specific Polycomb protein, are two major, known regulators of this process. Here, we show that RNF8 and SCML2 cooperate to regulate ubiquitination during meiosis, an early step to establish active histone modifications for subsequent gene activation. Double mutants of Rnf8 and Scml2 revealed that RNF8-dependent monoubiquitination of histone H2A at Lysine 119 (H2AK119ub) is deubiquitinated by SCML2, demonstrating interplay between RNF8 and SCML2 in ubiquitin regulation. Additionally, we identify distinct functions of RNF8 and SCML2 in the regulation of ubiquitination: SCML2 deubiquitinates RNF8-independent H2AK119ub but does not deubiquitinate RNF8-dependent polyubiquitination. RNF8-dependent polyubiquitination is required for the establishment of H3K27 acetylation, a marker of active enhancers, while persistent H2AK119ub inhibits establishment of H3K27 acetylation. Following the deposition of H3K27 acetylation, H3K4 dimethylation is established as an active mark on poised promoters. Together, we propose a model whereby regulation of ubiquitin leads to the organization of poised enhancers and promoters during meiosis, which induce subsequent gene activation from the otherwise silent sex chromosomes in postmeiotic spermatids.
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