Acidic patch histone mutations and their effects on nucleosome remodeling.
| Autor: | Dao HT; Department of Chemical Biology and Therapeutics, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, U.S.A., Pham LTD; Global Pediatric Medicine, St. Jude Children's Research Hospital, Memphis, Tennessee 38105, U.S.A. |
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| Jazyk: | angličtina |
| Zdroj: | Biochemical Society transactions [Biochem Soc Trans] 2022 Apr 29; Vol. 50 (2), pp. 907-919. |
| DOI: | 10.1042/BST20210773 |
| Abstrakt: | Structural and biochemical studies have identified a histone surface on each side of the nucleosome disk termed 'the nucleosome acidic patch' that acts as a regulatory hub for the function of numerous nuclear proteins, including ATP-dependent chromatin complexes (remodelers). Four major remodeler subfamilies, SWI/SNF, ISWI, CHD, and INO80, have distinct modes of interaction with one or both nucleosome acidic patches, contributing to their specific remodeling outcomes. Genome-wide sequencing analyses of various human cancers have uncovered high-frequency mutations in histone coding genes, including some that map to the acidic patch. How cancer-related acidic patch histone mutations affect nucleosome remodeling is mainly unknown. Recent advances in in vitro chromatin reconstitution have enabled access to physiologically relevant nucleosomes, including asymmetric nucleosomes that possess both wild-type and acidic patch mutant histone copies. Biochemical investigation of these substrates revealed unexpected remodeling outcomes with far-reaching implications for alteration of chromatin structure. This review summarizes recent findings of how different remodeler families interpret wild-type and mutant acidic patches for their remodeling functions and discusses models for remodeler-mediated changes in chromatin landscapes as a consequence of acidic patch mutations. (© 2022 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.) |
| Databáze: | MEDLINE |
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