Taghi-C Reveals 3D Chromatin Architecture Dynamics during Hematopoiesis

In mammalian cells, chromosomes are packaged in a micron-level nucleus, with each chromosome occupying a specific nuclear territory. Dynamic alterations in chromatin structures are associated with many biological processes, including cell cycle, differentiation and diseases. However, spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly due to the large numbers of starting cells required for current chromatin conformation capture approaches.

Here, we introduce a new Hi-C method, tagHi-C, to capture the chromatin structures of hundreds of cells. We showed that tagHi-C is a feasible approach to capture three-dimensional (3D) chromatin structures using hundreds of cells within only two days. Using our improved technique, we were able to map the spatiotemporal dynamics of chromatin structure in 10 primary hematopoietic stem, progenitor and differentiated cell populations from mouse bone marrow.

Our results revealed that significant differences in chromatin condensation in hematopoietic cells. We found changes in compartment organization and the Rabl configurations occur during hematopoietic cell differentiation. We identified gene-body associating domains (GADs) as general structures for highly expressed genes. Moreover, we linked genome-wide association studies (GWAS) loci to distal new genes through spatial chromatin looping, which extend the body of knowledge how GWAS loci influence gene expression through spatial chromatin folding aspect.