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The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation

Author

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  • Wenyi Mi

    (The University of Texas MD Anderson Cancer Center
    Van Andel Research Institute)

  • Yi Zhang

    (University of Colorado School of Medicine)

  • Jie Lyu

    (Baylor College of Medicine)

  • Xiaolu Wang

    (The University of Texas MD Anderson Cancer Center
    Van Andel Research Institute)

  • Qiong Tong

    (University of Colorado School of Medicine)

  • Danni Peng

    (The University of Texas MD Anderson Cancer Center)

  • Yongming Xue

    (The University of Texas MD Anderson Cancer Center)

  • Adam H. Tencer

    (University of Colorado School of Medicine)

  • Hong Wen

    (The University of Texas MD Anderson Cancer Center
    Van Andel Research Institute)

  • Wei Li

    (Baylor College of Medicine)

  • Tatiana G. Kutateladze

    (University of Colorado School of Medicine)

  • Xiaobing Shi

    (The University of Texas MD Anderson Cancer Center
    Van Andel Research Institute)

Abstract

Recognition of histones by epigenetic readers is a fundamental mechanism for the regulation of chromatin and transcription. Most reader modules target specific post-translational modifications on histones. Here, we report the identification of a reader of histone H3, the ZZ-type zinc finger (ZZ) domain of ZZZ3, a subunit of the Ada-two-A-containing (ATAC) histone acetyltransferase complex. The solution NMR structure of the ZZ in complex with the H3 peptide reveals a unique binding mechanism involving caging of the N-terminal Alanine 1 of histone H3 in an acidic cavity of the ZZ domain, indicating a specific recognition of H3 versus other histones. Depletion of ZZZ3 or disruption of the ZZ-H3 interaction dampens ATAC-dependent promoter histone H3K9 acetylation and target gene expression. Overall, our study identifies the ZZ domain of ZZZ3 as a histone H3 reader that is required for the ATAC complex-mediated maintenance of histone acetylation and gene activation.

Suggested Citation

  • Wenyi Mi & Yi Zhang & Jie Lyu & Xiaolu Wang & Qiong Tong & Danni Peng & Yongming Xue & Adam H. Tencer & Hong Wen & Wei Li & Tatiana G. Kutateladze & Xiaobing Shi, 2018. "The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation," Nature Communications, Nature, vol. 9(1), pages 1-9, December.
    • Handle: RePEc:nat:natcom:v:9:y:2018:i:1:d:10.1038_s41467-018-06247-5
    DOI: 10.1038/s41467-018-06247-5
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