CTCF is selectively required for maintaining chromatin accessibility and gene expression in human erythropoiesis [RNA-seq]

The three-dimensional chromatin niche provides a precise gene expression control of cell identity, differentiation, and disease development. CTCF is considered as the most essential transcription factor regulating chromatin architecture and gene expression. However, the genome-wide impact of CTCF in erythropoiesis has not been extensively investigated yet. To further study the direct transcriptional regulatory role of CTCF, we established two endogenous C-terminus AID-CTCF system in t human erythroblast cell lines and systematically investigated the effects of acute CTCF loss by auxin-inducible degron system on transcriptional programs and chromatin accessibility. By integrating multi-omics datasets, we revealed that acute CTCF loss notably suppressed the subset of GATA1 downstream targets. Importantly, we revealed that acute CTCF loss notably disrupted genome-wide chromatin accessibility and transcription network. Importantly, we identified that over thousands of chromatin accessibility regions were decreased while only a few hundreds of increased regions after depletion of CTCF in both HUDEP-2 and HEL lines, suggesting the role of CTCF in maintaining the proper chromatin openness in erythroid lineage. Moreover, CTCF depletion in erythroid context significantly disrupted TAD boundary integrity and chromatin loops while not affecting the nuclear compartmentalization. In summary, our results addressed a novel role of CTCF in regulating erythroid differentiation by maintaining its proper chromatin openness, which will undoubtedly extend our understanding of CTCF biology.