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YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer

Author

Listed:
  • Wenyi Mi

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center)

  • Haipeng Guan

    (MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University)

  • Jie Lyu

    (Dan L. Duncan Cancer Center, Baylor College of Medicine)

  • Dan Zhao

    (MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University)

  • Yuanxin Xi

    (Dan L. Duncan Cancer Center, Baylor College of Medicine)

  • Shiming Jiang

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center)

  • Forest H. Andrews

    (University of Colorado School of Medicine)

  • Xiaolu Wang

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center)

  • Mihai Gagea

    (The University of Texas M.D. Anderson Cancer Center)

  • Hong Wen

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center)

  • Laszlo Tora

    (Institut de Génétique et de Biologie Moléculaire et Cellulaire
    Centre National de la Recherche Scientifique, UMR7104
    Institut National de la Santé et de la Recherche Médicale, U964
    Université de Strasbourg)

  • Sharon Y. R. Dent

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center
    Genes and Development and Epigenetics & Molecular Carcinogenesis Graduate Programs, The University of Texas Graduate School of Biomedical Sciences)

  • Tatiana G. Kutateladze

    (University of Colorado School of Medicine)

  • Wei Li

    (Dan L. Duncan Cancer Center, Baylor College of Medicine)

  • Haitao Li

    (MOE Key Laboratory of Protein Sciences, Beijing Advanced Innovation Center for Structural Biology, Department of Basic Medical Sciences, School of Medicine, Tsinghua University
    Tsinghua-Peking Joint Center for Life Sciences, Tsinghua University)

  • Xiaobing Shi

    (The University of Texas M.D. Anderson Cancer Center
    Center for Cancer Epigenetics, The University of Texas M.D. Anderson Cancer Center
    Genes and Development and Epigenetics & Molecular Carcinogenesis Graduate Programs, The University of Texas Graduate School of Biomedical Sciences)

Abstract

Recognition of modified histones by “reader” proteins constitutes a key mechanism regulating diverse chromatin-associated processes important for normal and neoplastic development. We recently identified the YEATS domain as a novel acetyllysine-binding module; however, the functional importance of YEATS domain-containing proteins in human cancer remains largely unknown. Here, we show that the YEATS2 gene is highly amplified in human non-small cell lung cancer (NSCLC) and is required for cancer cell growth and survival. YEATS2 binds to acetylated histone H3 via its YEATS domain. The YEATS2-containing ATAC complex co-localizes with H3K27 acetylation (H3K27ac) on the promoters of actively transcribed genes. Depletion of YEATS2 or disruption of the interaction between its YEATS domain and acetylated histones reduces the ATAC complex-dependent promoter H3K9ac levels and deactivates the expression of essential genes. Taken together, our study identifies YEATS2 as a histone H3K27ac reader that regulates a transcriptional program essential for NSCLC tumorigenesis.

Suggested Citation

  • Wenyi Mi & Haipeng Guan & Jie Lyu & Dan Zhao & Yuanxin Xi & Shiming Jiang & Forest H. Andrews & Xiaolu Wang & Mihai Gagea & Hong Wen & Laszlo Tora & Sharon Y. R. Dent & Tatiana G. Kutateladze & Wei Li, 2017. "YEATS2 links histone acetylation to tumorigenesis of non-small cell lung cancer," Nature Communications, Nature, vol. 8(1), pages 1-14, December.
    • Handle: RePEc:nat:natcom:v:8:y:2017:i:1:d:10.1038_s41467-017-01173-4
    DOI: 10.1038/s41467-017-01173-4
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    Cited by:

    1. Zhe Wang & Xin Yang & Delin Chen & Yanqing Liu & Zhiming Li & Shoufu Duan & Zhiguo Zhang & Xuejun Jiang & Brent R. Stockwell & Wei Gu, 2024. "GAS41 modulates ferroptosis by anchoring NRF2 on chromatin," Nature Communications, Nature, vol. 15(1), pages 1-16, December.

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