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
  • 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.