GSE201821
CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis [H2_ATAC]
The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the master transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF has not been extensively investigated due to the lack of proper research tools. Here, using a state-of-the-art auxin-inducible degron cellular model built up in human erythroid progenitors, we investigated the effects of acute CTCF loss on transcriptional programs and chromatin accessibility during human erythroid maturation. By integrating multi-omics datasets, we revealed that CTCF acute loss significantly disrupted genome-wide chromatin accessibility and transcription network. We further identified several direct novel target genes of CTCF in erythroid progenitor cells, including one master transcription factor GATA2 in hematopoiesis. Acute depletion of CTCF protein or disrupting CTCF binding sites in the topologically associated domains (TAD) boundary region of the GATA2 locus results in a significant transcriptional increase of GATA2. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation, which will undoubtedly extend our understanding of CTCF biology. Overall design: Integrative analysis HiC/ATAC/RNA/ChIP-seq in HUDEP2 with or without acute degradation of CTCF.