Characterization of chromosome organization in the differentiation of acute myeloid leukemia cells by all-trans retinoic acid

Abstract

A concomitant change of nucleus shape and chromosome conformation often happens in all-trans retinoic acid (ATRA)-induced differentiation of acute myeloid leukemia cells. However, the relation between the 3D chromosome architecture and the genome-wide epigenetic pattern for transcriptional regulation is poorly understood. In this study, high-throughput chromosome conformation capture (Hi-C) and chromosome immunoprecipitation (ChIP-seq) were employed to investigate the landscape of chromosome distal interaction and H3K4/27me3 in HL-60 cells treated with ATRA. We observed a general loss of topological associated domains (TADs) at PTPN11 during the differentiation of HL-60 cells. Furthermore, the significantly reduced enrichment of CCCTC binding factor (CTCF) near the boundary where PTPN11 located, as well as the decreased H3K4me3 and increased H3K27me3 enrichment at PTPN11 upon ATRA treatment was observed. Taken together, our study indicated a regulatory mechanism behind the silenced PTPN11 in HL-60 cells differentiation.