TCF-1 mediates 3D genome reconfiguration during T cell development (HiChIP)

Lineage-determine transcription factors (LDTFs) can determine gene expression programs of a specific cell type, by rewiring the linear regulatory network. However, it's not clear whether and how LDTFs can alter the 3D genome organization during development. Here, we investigated the effect of T cell factor 1 (TCF-1) on the reconfiguration of 3D genome during T cell development. Topologically associated domains (TADs) that have higher density of TCF-1 gain more intra-TAD interactions during T cell development. TCF-1 colocalized with CCCTC-binding factor (CTCF) substantially reduced the insulation and increased the local interactions, which additionally have stronger interactions with T cell development genes. We further found that a considerable number of boundaries are lost during T cell development, and that TCF-1 is enriched at the lost boundaries, including the ones near key T cell development genes. Overexpression of TCF-1 in fibroblast demonstrates that both high density of TCF-1 and TCF-1 colocalized with CTCF can optimally increase the local interactions. Correspondingly, knocking out of TCF-1 in DN3 cell line leads to decreased intra-TAD interactions and gain of insulation at some of its binding sites. Finally, we found that TCF-1 can recruit and maintain cohesin at its binding sites, which probably cause reconfiguration of the 3D genome. Taken together, our study shows that TCF-1 can change the 3D genome at both TAD level and finer scale potentially through the recruitment of cohesin. Overall design: Study the 3D genome reorganization mediated by TCF-1