Open AccessNMR Analyses of Acetylated H2A.Z Isoforms Identify Differential Binding Interactions with the Bromodomain of the NURF Nucleosome Remodeling Complex
Author(s) -
Noelle M. Olson,
Samantha Kroc,
Jennifer J. Johnson,
Huda Zahid,
Peter D. Ycas,
A. Chan,
Jennifer R Kimbrough,
Prakriti Kalra,
E. Schönbrunn,
William C. Pomerantz
Publication year - 2020
Publication title -
biochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.43
H-Index - 253
eISSN - 1520-4995
pISSN - 0006-2960
DOI - 10.1021/acs.biochem.0c00159
Subject(s) - bromodomain , acetylation , histone , nucleosome , chromatin , phd finger , chromatin remodeling , chemistry , lysine , biochemistry , gene isoform , brd4 , biology , microbiology and biotechnology , gene , transcription factor , amino acid , zinc finger
Gene specific recruitment of bromodomain-containing proteins to chromatin is affected by post-translational acetylation of lysine on histones. Whereas interactions of the bromodomain with acetylation patterns of native histones (H2A, H2B, H3, and H4) have been well characterized, the motif for recognition for histone variants H2A.Z I and H2A.Z II by bromodomains has yet to be fully investigated. Elucidating these molecular mechanisms is crucial for understanding transcriptional regulation in cellular processes involved in both development and disease. Here, we have used protein-observed fluorine NMR to fully characterize the affinities of H2A.Z I and II acetylation patterns for BPTF's bromodomain and found the diacetylated mark of lysine 7 and 13 on H2A.Z II to have the strongest interaction with K7ac preferentially engaging the binding site. We further examined the selectivity of H2A.Z histones against a variety of bromodomains, revealing that the bromodomain of CECR2 binds with the highest affinity and specificity for acetylated H2A.Z I over isoform II. These results support a possible role for different H2A.Z transcriptional activation mechanisms that involve recruitment of chromatin remodeling complexes.