biostudies-literatureMi WU.S. Department of Health & Human Services | NIH | National Cancer Institute (NCI)U.S. Department of Health & Human Services | NIH | National Institute of General Medical SciencesCancer Prevention and Research Institute of Texas (Cancer Prevention Research Institute of Texas)Cancer Prevention and Research Institute of TexasU.S. Department of Health & Human Services | NIH | National Institute of General Medical Sciences (NIGMS)Leukemia and Lymphoma Society (LLS)U.S. Department of Health & Human Services | NIH | National Cancer InstituteNHGRI NIH HHSNCI NIH HHSU.S. Department of Health & Human Services | National Institutes of Health (NIH)U.S. Department of Health & Human Services | National Institutes of HealthNIGMS NIH HHSLeukemia and Lymphoma Society3759https://www.ebi.ac.uk/biostudies/studies/S-EPMC6138639biostudies-literatureUnknown9(1)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. OvNature communicationsThe ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation.PMC6138639R01 GM125195CA204020GM106416R01 GM1064161339-17RP160739R01 GM100907R01 CA204020R01 HG007538R01 CA193466GM125195RP160237HG007538CA193466GM100907Li WWen HTong QPeng DLyu JZhang YMi WWang XKutateladze TGShi XXue YTencer AHfalseThe ZZ-type zinc finger of ZZZ3 modulates the ATAC complex-mediated histone acetylation and gene activation.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. Ov2018-01-01T00:00:00Z2018 Sep2026-04-30T01:58:44.123Z2019-03-26T23:56:15ZS-EPMC61386393021797810.1038/s41467-018-06247-5