3D Chromatin organization of signal-induced specific enhancers safeguards early ESC differentiation by promoting cluster gene expression [Hi-ChIP]

Here, by integrating bulk RNA sequencing, single-cell RNA sequencing, 4D-SmartDIA quantitative proteomics data, and a CRISPR/Cas9-mediated RA receptor deletion model, we find that RA signaling-induced early ESC differentiation is multilineage.

During early ESC differentiation, in the context of attenuated and enhanced RA signaling, we identified Cyp26 and HoxB cluster genes as its direct downstream targets. Upon activation of RA signaling, RA receptors induce new specific enhancers in the proximal/distal regions of cluster gene loci, whereas inhibition of RA signaling significantly reduces proximal/distal enhancer activity, chromatin accessibility and cluster gene expression.