Department of Biomedical Genetics, Wilmot Cancer Institute, University of Rochester Medical Center, Rochester, NY, USA.
Nat Commun. 2020 Oct 8;11(1):5063. doi: 10.1038/s41467-020-18821-x.
Genome-wide chromatin state underlies gene expression potential and cellular function. Epigenetic features and nucleosome positioning contribute to the accessibility of DNA, but widespread regulators of chromatin state are largely unknown. Our study investigates how coordination of ANP32E and H2A.Z contributes to genome-wide 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 at promoters in a hierarchical manner. H2A.Z initially localizes downstream of the transcription start site, and if H2A.Z is already present downstream, additional H2A.Z accumulates upstream. This hierarchical H2A.Z accumulation coincides with improved nucleosome positioning, heightened transcription factor binding, and increased expression of neighboring genes. Thus, ANP32E dramatically influences genome-wide chromatin accessibility through subtle refinement of H2A.Z patterns, providing a means to reprogram chromatin state and to hone gene expression levels.
基因组范围的染色质状态是基因表达潜力和细胞功能的基础。表观遗传特征和核小体定位有助于 DNA 的可及性，但广泛的染色质状态调节剂在很大程度上是未知的。我们的研究调查了 ANP32E 和 H2A.Z 的协调如何有助于小鼠成纤维细胞的全基因组染色质状态。我们将 H2A.Z 定义为通用的染色质可及性因子，并证明 ANP32E 拮抗 H2A.Z 的积累以限制全基因组的染色质可及性。在没有 ANP32E 的情况下，H2A.Z 以分层的方式在启动子处积累。H2A.Z 最初位于转录起始位点的下游，如果 H2A.Z 已经存在于下游，那么额外的 H2A.Z 会积累在上游。这种分层的 H2A.Z 积累与核小体定位的改善、转录因子结合的增强以及相邻基因表达水平的提高相吻合。因此，ANP32E 通过对 H2A.Z 模式的细微细化，显著影响全基因组的染色质可及性，为重新编程染色质状态和调整基因表达水平提供了一种手段。
