GATA Switch Enhancers Mark Dynamically Regulated Chromatin Interaction Nodes during Erythroid Maturation. GATA Switch Enhancers Mark Dynamically Regulated Chromatin Interaction Nodes during Erythroid Maturation

Erythropoiesis is among the best understood examples of cell differentiation. In a required step, GATA1 replaces GATA2 at genomic loci, termed GATA switch enhancers. Little is known about how this switch affects chromatin architecture. Here, we show that cohesin binds GATA1 and occupies most GATA switch enhancers. Cohesin-based chromatin interaction analysis demonstrated that the most dynamic and interactive enhancers are enriched for GATA switch sites/TAL1 occupancy and frequently lack super-enhancer features. A c-kit locus CRISPR/Cas9 screen identified GATA motifs within one such element as strongly impacting expression. These data highlight the role of developmentally exchanged transcription factors in modulating genomic folding. Overall design: Epigenetic profiling of erythroid differentiation

红细胞生成（Erythropoiesis）是目前研究最为透彻的细胞分化范例之一。在其关键步骤中，GATA1会在被称为GATA开关增强子（GATA switch enhancers）的基因组位点上取代GATA2。目前学界对这一替换如何影响染色质架构仍知之甚少。本研究证实，黏连蛋白（cohesin）可与GATA1结合，并富集于绝大多数GATA开关增强子区域。基于黏连蛋白的染色质相互作用分析显示，动态性与互作活性最强的增强子显著富集GATA开关位点与TAL1结合区域，且通常不具备超级增强子（super-enhancer）的典型特征。针对c-kit基因座的CRISPR/Cas9筛选实验表明，此类调控元件内的GATA基序对基因表达具有极强的调控作用。上述研究结果凸显了发育进程中发生替换的转录因子在调控基因组折叠过程中的关键作用。实验整体设计：红细胞分化的表观遗传谱分析。