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.
The flower represents the Drosophila testis niche with the hub cells at the center. Each petal of the flower represents Germline stem cells (GSCs) with a large and a smaller purple circle representing centromere; green rays representing stronger centromeres preferentially attach to the niche. Red and green caterpillars represent sister chromatids in prometaphase with separable old and new H3 in GSCs. Further, large butterflies closer to the flower represent prometaphase GSCs with a red wing vs a green wing representing non-overlapping old and new H3. Small orange butterflies away from the flower represent prophase gonialblast cells with overlapping old and new H3 signals. The background is from coiled sperm from the fly testis. Cover art generated by Professor Tim Phelps.
Acidic patch histone mutations and their effects on nucleosome remodeling
Hai T. Dao, Linh T. D. Pham; Acidic patch histone mutations and their effects on nucleosome remodeling. Biochem Soc Trans 29 April 2022; 50 (2): 907–919. doi: https://doi.org/10.1042/BST20210773
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