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Role of histone H2A ubiquitination in Polycomb silencing

Author

Listed:
  • Hengbin Wang

    (University of North Carolina at Chapel Hill)

  • Liangjun Wang

    (Southern Methodist University)

  • Hediye Erdjument-Bromage

    (Memorial Sloan Kettering Cancer Center)

  • Miguel Vidal

    (Centro de Investigaciones Biologicas)

  • Paul Tempst

    (Memorial Sloan Kettering Cancer Center)

  • Richard S. Jones

    (Southern Methodist University)

  • Yi Zhang

    (University of North Carolina at Chapel Hill)

Abstract

Covalent modification of histones is important in regulating chromatin dynamics and transcription1,2. One example of such modification is ubiquitination, which mainly occurs on histones H2A and H2B3. Although recent studies have uncovered the enzymes involved in histone H2B ubiquitination4,5,6 and a ‘cross-talk’ between H2B ubiquitination and histone methylation7,8, the responsible enzymes and the functions of H2A ubiquitination are unknown. Here we report the purification and functional characterization of an E3 ubiquitin ligase complex that is specific for histone H2A. The complex, termed hPRC1L (human Polycomb repressive complex 1-like), is composed of several Polycomb-group proteins including Ring1, Ring2, Bmi1 and HPH2. hPRC1L monoubiquitinates nucleosomal histone H2A at lysine 119. Reducing the expression of Ring2 results in a dramatic decrease in the level of ubiquitinated H2A in HeLa cells. Chromatin immunoprecipitation analysis demonstrated colocalization of dRing with ubiquitinated H2A at the PRE and promoter regions of the Drosophila Ubx gene in wing imaginal discs. Removal of dRing in SL2 tissue culture cells by RNA interference resulted in loss of H2A ubiquitination concomitant with derepression of Ubx. Thus, our studies identify the H2A ubiquitin ligase, and link H2A ubiquitination to Polycomb silencing.

Suggested Citation

  • Hengbin Wang & Liangjun Wang & Hediye Erdjument-Bromage & Miguel Vidal & Paul Tempst & Richard S. Jones & Yi Zhang, 2004. "Role of histone H2A ubiquitination in Polycomb silencing," Nature, Nature, vol. 431(7010), pages 873-878, October.
  • Handle: RePEc:nat:nature:v:431:y:2004:i:7010:d:10.1038_nature02985
    DOI: 10.1038/nature02985
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    Citations

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    Cited by:

    1. Daniel Bsteh & Hagar F. Moussa & Georg Michlits & Ramesh Yelagandula & Jingkui Wang & Ulrich Elling & Oliver Bell, 2023. "Loss of cohesin regulator PDS5A reveals repressive role of Polycomb loops," Nature Communications, Nature, vol. 14(1), pages 1-16, December.
    2. Wenjing Yan & Yongwang Zhong & Xin Hu & Tuan Xu & Yinghua Zhang & Stephen Kales & Yanyan Qu & Daniel C. Talley & Bolormaa Baljinnyam & Christopher A. LeClair & Anton Simeonov & Brian M. Polster & Ruil, 2023. "Auranofin targets UBA1 and enhances UBA1 activity by facilitating ubiquitin trans-thioesterification to E2 ubiquitin-conjugating enzymes," Nature Communications, Nature, vol. 14(1), pages 1-17, December.
    3. Yanjiang Liu & Gongcheng Hu & Shengxiong Yang & Mingze Yao & Zicong Liu & Chenghong Yan & Yulin Wen & Wangfang Ping & Juehan Wang & Yawei Song & Xiaotao Dong & Guangjin Pan & Hongjie Yao, 2023. "Functional dissection of PRC1 subunits RYBP and YAF2 during neural differentiation of embryonic stem cells," Nature Communications, Nature, vol. 14(1), pages 1-14, December.
    4. Mengwen Hu & Yu-Han Yeh & Yasuhisa Munakata & Hironori Abe & Akihiko Sakashita & So Maezawa & Miguel Vidal & Haruhiko Koseki & Neil Hunter & Richard M. Schultz & Satoshi H. Namekawa, 2022. "PRC1-mediated epigenetic programming is required to generate the ovarian reserve," Nature Communications, Nature, vol. 13(1), pages 1-10, December.
    5. Yu Zhang & Min Ma & Meng Liu & Aiqing Sun & Xiaoyun Zheng & Kunpeng Liu & Chunmei Yin & Chuanshun Li & Cizhong Jiang & Xiaoyu Tu & Yuda Fang, 2023. "Histone H2A monoubiquitination marks are targeted to specific sites by cohesin subunits in Arabidopsis," Nature Communications, Nature, vol. 14(1), pages 1-12, December.
    6. Anna Worthmann & Julius Ridder & Sharlaine Y. L. Piel & Ioannis Evangelakos & Melina Musfeldt & Hannah Voß & Marie O’Farrell & Alexander W. Fischer & Sangeeta Adak & Monica Sundd & Hasibullah Siffeti , 2024. "Fatty acid synthesis suppresses dietary polyunsaturated fatty acid use," Nature Communications, Nature, vol. 15(1), pages 1-13, December.
    7. Xinyi Chen & Yiran Guo & Ting Zhao & Jiuwei Lu & Jian Fang & Yinsheng Wang & Gang Greg Wang & Jikui Song, 2024. "Structural basis for the H2AK119ub1-specific DNMT3A-nucleosome interaction," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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