NMR Analyses of Acetylated H2A.Z Isoforms Identify Differential Binding Interactions with the Bromodomain of the NURF Nucleosome Remodeling Complex.

Autor:	Olson NM; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Kroc S; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Johnson JA; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Zahid H; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Ycas PD; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Chan A; Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, United States., Kimbrough JR; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Kalra P; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States., Schönbrunn E; Drug Discovery Department, H. Lee Moffitt Cancer Center and Research Institute, 12902 Magnolia Drive, Tampa, Florida 33612, United States., Pomerantz WCK; Department of Chemistry, University of Minnesota, 207 Pleasant Street Southeast, Minneapolis, Minnesota 55455, United States.
Jazyk:	angličtina
Zdroj:	Biochemistry [Biochemistry] 2020 May 26; Vol. 59 (20), pp. 1871-1880. Date of Electronic Publication: 2020 May 11.
DOI:	10.1021/acs.biochem.0c00159
Abstrakt:	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.
Databáze:	MEDLINE
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