Pre-existing chromatin accessibility of switchable repressive compartment delineates cell plasticity

Cell plasticity endows differentiated cells with competence to be reprogrammed to other lineages. Although extrinsic factors driving cell-identity conversion have been extensively characterized, it remains elusive which intrinsic epigenetic attributes, including high-order chromatin organization, delineate cell plasticity. By analysing the transcription-factor-induced transdifferentiation from fibroblasts to hepatocytes, we uncovered contiguous compartment-switchable regions (CSRs) as a unique chromatin unit. Specifically, compartment B-to-A CSRs, enriched with hepatic genes, possessed a mosaic status of inactive chromatin and pre-existing and continuous accessibility in fibroblasts. Pre-existing accessibility enhanced the binding of inducible factor Foxa3, which triggered epigenetic activation and chromatin interaction as well as hepatic gene expression. Notably, these changes were restrained within B-to-A CSR boundaries that were defined by CTCF occupancy. Moreover, such chromatin organization and mosaic status were detectable in different cell types and involved in multiple reprogramming processes, suggesting an intrinsic chromatin attribute in understanding cell plasticity.

Automated summary

Cell plasticity, the ability for cells to be reprogrammed, is determined by intrinsic epigenetic attributes such as chromatin organization. Researchers discovered a unique chromatin unit called contiguous compartment-switchable regions (CSRs), which play a crucial role in cell identity conversion. Specifically, CSRs with a switch from compartment B to A had a mosaic status of inactive chromatin and pre-existing accessibility, and this attribute facilitated the binding of inducible factor Foxa3, leading to epigenetic activation and gene expression. This chromatin organization was found in various cell types and involved in multiple reprogramming processes, highlighting the importance of understanding intrinsic chromatin attributes in cell plasticity.