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ANP32E Restricts Widespread Chromatin Accessibility Through Regulation of H2A.Z [RNA-seq]

ABSTRACT: Genome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning are major factors in determining chromatin accessibility. Our study investigates how genomic localization of the histone variant H2A.Z regulates chromatin state in mouse fibroblasts. We define H2A.Z as a universal chromatin accessibility factor, and demonstrate that ANP32E antagonizes H2A.Z accumulation to restrict chromatin accessibility genome-wide. In the absence of ANP32E, H2A.Z accumulates in a hierarchical manner at promoters. H2A.Z initially localizes at the +1 nucleosome, and then if H2A.Z is already present at the +1 nucleosome position in WT, additional H2A.Z accumulates at the -1 nucleosome position. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor footprint protection, and increased expression for neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.

ORGANISM(S): Mus musculus

PROVIDER: GSE145704 | GEO | 2020/09/08

REPOSITORIES: GEO

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