GATA-1-dependent histone H3K27ac mediates erythroid cell-specific interaction between CTCF sites

CTCF sites interact with each other in the chromatin environment, establishing domains. Our previous study showed that interaction between CTCF sites is cell type-specific around the β-globin locus and is dependent on erythroid specific activator GATA-1. To find out molecular mechanisms of the cell type-specific interaction, we directly inhibited GATA-1 binding to the β-globin enhancers by deleting its binding motifs and found that histone H3K27 acetylation (H3K27ac) was decreased at CTCF sites surrounding the β-globin locus, even though CTCF binding itself was maintained at the sites. Forced H3K27ac by TSA treatment or CBP/p300 KD affected the interactions between CTCF sites around the β-globin locus. Analysis of public ChIA-PET data revealed that H3K27ac is higher at CTCF sites forming short chromatin interactions than long interactions. The short interactions contain erythropoiesis-associated genes and GATA-1 binding sites in erythroid K562 cells. Depletion of GATA-1 reduced H3K27ac at CTCF sites near erythroid enhancers. These results indicate that GATA-1-dependent histone H3K27ac at neighboring CTCF sites mediates erythroid specific chromatin interaction between them.