show Abstracthide AbstractErythropoiesis 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