2. Academic Validation
  3. The ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation

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

  • Nat Commun. 2018 Sep 14;9(1):3759. doi: 10.1038/s41467-018-06247-5.
Wenyi Mi 1 2,  Yi Zhang 3,  Jie Lyu 4,  Xiaolu Wang 1 2,  Qiong Tong 3,  Danni Peng 1,  Yongming Xue 1,  Adam H Tencer 3,  Hong Wen 1 2,  Wei Li 4,  Tatiana G Kutateladze 5,  Xiaobing Shi 6 7
Affiliations

Affiliations

  • 1 Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA.
  • 2 Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, 49503, USA.
  • 3 Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, 80045, USA.
  • 4 Dan L. Duncan Cancer Center, Department of Molecular and Cellular Biology, Baylor College of Medicine, Houston, Texas, 77030, USA.
  • 5 Department of Pharmacology, University of Colorado School of Medicine, Aurora, Colorado, 80045, USA. [email protected].
  • 6 Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, The University of Texas MD Anderson Cancer Center, Houston, Texas, 77030, USA. [email protected].
  • 7 Center for Epigenetics, Van Andel Research Institute, Grand Rapids, Michigan, 49503, USA. [email protected].
PMID: 30217978 DOI: 10.1038/s41467-018-06247-5
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.

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