tagHi-C Reveals 3D Chromatin Architecture Dynamics during Mouse Hematopoiesis

Spatiotemporal chromatin reorganization during hematopoietic differentiation has not been comprehensively characterized, mainly because of the large numbers of starting cells required for current chromatin conformation capture approaches. Here, we introduce a low-input tagmentation-based Hi-C (tagHi-C) method to capture the chromatin structures of hundreds of cells. Using tagHi-C, we are able to map the spatiotemporal dynamics of chromatin structure in ten primary hematopoietic stem, progenitor, and differentiated cell populations from mouse bone marrow. Our results reveal that changes in compartment dynamics and the Rabl configuration occur during hematopoietic cell differentiation. We identify gene-body-associating domains (GADs) as general structures for highly expressed genes. Moreover, we extend the body of knowledge regarding genes influenced by genome-wide association study (GWAS) loci through spatial chromatin looping. Our study provides the tagHi-C method for studying the three-dimensional (3D) genome of a small number of cells and maps the comprehensive 3D chromatin landscape of bone marrow hematopoietic cells. [Display omitted] •Low-input tagHi-C captures the chromatin structures using hundreds of cells•Compartment and the Rabl configuration are dynamic during hematopoiesis•Gene-body-associating domains (GADs) are general structures of highly expressed genes•Spatial chromatin loops link GWAS SNPs to candidate blood-phenotype genes Zhang et al. develop a low-input, tagmentation-based Hi-C method (tagHi-C) to map the chromatin architecture during hematopoietic differentiation. Their findings uncover the spatiotemporal dynamics of various chromatin structures in hematopoietic cells.