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Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors

Author

Listed:
  • Chong Wang

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Luyao Zhang

    (Brigham and Women’s Hospital and Harvard Medical School
    The First Affiliated Hospital, Sun Yat-Sen University)

  • Liangru Ke

    (Brigham and Women’s Hospital and Harvard Medical School
    Sun Yat-Sen Cancer Center, Sun Yat-Sen University)

  • Weiyue Ding

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Sizun Jiang

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Difei Li

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Yohei Narita

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Isabella Hou

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Jun Liang

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Shijun Li

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Haipeng Xiao

    (The First Affiliated Hospital, Sun Yat-Sen University)

  • Eva Gottwein

    (Feinberg School of Medicine, Northwestern University)

  • Kenneth M. Kaye

    (Brigham and Women’s Hospital and Harvard Medical School)

  • Mingxiang Teng

    (H. Lee Moffitt Cancer Center and Research Institute)

  • Bo Zhao

    (Brigham and Women’s Hospital and Harvard Medical School)

Abstract

Primary effusion lymphoma (PEL) has a very poor prognosis. To evaluate the contributions of enhancers/promoters interactions to PEL cell growth and survival, here we produce H3K27ac HiChIP datasets in PEL cells. This allows us to generate the PEL enhancer connectome, which links enhancers and promoters in PEL genome-wide. We identify more than 8000 genomic interactions in each PEL cell line. By incorporating HiChIP data with H3K27ac ChIP-seq data, we identify interactions between enhancers/enhancers, enhancers/promoters, and promoters/promoters. HiChIP further links PEL super-enhancers to PEL dependency factors MYC, IRF4, MCL1, CCND2, MDM2, and CFLAR. CRISPR knock out of MEF2C and IRF4 significantly reduces MYC and IRF4 super-enhancer H3K27ac signal. Knock out also reduces MYC and IRF4 expression. CRISPRi perturbation of these super-enhancers by tethering transcription repressors to enhancers significantly reduces target gene expression and reduces PEL cell growth. These data provide insights into PEL molecular pathogenesis.

Suggested Citation

  • Chong Wang & Luyao Zhang & Liangru Ke & Weiyue Ding & Sizun Jiang & Difei Li & Yohei Narita & Isabella Hou & Jun Liang & Shijun Li & Haipeng Xiao & Eva Gottwein & Kenneth M. Kaye & Mingxiang Teng & Bo, 2020. "Primary effusion lymphoma enhancer connectome links super-enhancers to dependency factors," Nature Communications, Nature, vol. 11(1), pages 1-13, December.
    • Handle: RePEc:nat:natcom:v:11:y:2020:i:1:d:10.1038_s41467-020-20136-w
    DOI: 10.1038/s41467-020-20136-w
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    Cited by:

    1. Sinan Xiong & Jianbiao Zhou & Tze King Tan & Tae-Hoon Chung & Tuan Zea Tan & Sabrina Hui-Min Toh & Nicole Xin Ning Tang & Yunlu Jia & Yi Xiang See & Melissa Jane Fullwood & Takaomi Sanda & Wee-Joo Chn, 2024. "Super enhancer acquisition drives expression of oncogenic PPP1R15B that regulates protein homeostasis in multiple myeloma," Nature Communications, Nature, vol. 15(1), pages 1-21, December.

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