Int J Biol Sci 2018; 14(11):1571-1585. doi:10.7150/ijbs.25328
Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis
1. Institute of Animal Genetics and Breeding, College of Animal Science and Technology, Sichuan Agricultural University, Chengdu 611130, China;
2. Farm Animal Genetic Resources Exploration and Innovation Key Laboratory of Sichuan Province, Sichuan Agricultural University, Chengdu 611130, China;
3. Novogene Bioinformatics Institute, Beijing 100089, China;
4. Chongqing Academy of Animal Sciences, Chongqing 402460, China;
5. Animal Breeding and Genetics Key Laboratory of Sichuan Province, Pig Science Institute, Sichuan Animal Science Academy, Chengdu 610066, China.
*These authors contributed equally to this work.
The recently developed high-throughput chromatin conformation capture (Hi-C) technology enables us to explore the spatial architecture of genomes, which is increasingly considered an important regulator of gene expression. To investigate the changes in three-dimensional (3D) chromatin structure and its mediated gene expression during adipogenesis and myogenesis, we comprehensively mapped 3D chromatin organization for four cell types (3T3-L1 pre-adipocytes, 3T3-L1-D adipocytes, C2C12 myoblasts, and C2C12-D myotubes). We demonstrate that the dynamic spatial genome architecture affected gene expression during cell differentiation. A considerable proportion (~22%) of the mouse genome underwent compartment A/B rearrangement during adipogenic and myogenic differentiation, and most (~80%) upregulated marker genes exhibited an active chromatin state with B to A switch or stable A compartment. More than half (65.4%-73.2%) of the topologically associating domains (TADs) are dynamic. The newly formed TAD and intensified local interactions in the Fabp gene cluster indicated more precise structural regulation of the expression of pro-differentiation genes during adipogenesis. About half (32.39%-59.04%) of the differential chromatin interactions (DCIs) during differentiation are promoter interactions, although these DCIs only account for a small proportion of genome-wide interactions (~9.67% in adipogenesis and ~4.24% in myogenesis). These differential promoter interactions were enriched with promoter-enhancer interactions (PEIs), which were mediated by typical adipogenic and myogenic transcription factors. Differential promoter interactions also included more differentially expressed genes than nonpromoter interactions. Our results provide a global view of dynamic chromatin interactions during adipogenesis and myogenesis and are a resource for studying long-range chromatin interactions mediating the expression of pro-differentiation genes.
Keywords: Adipogenesis, Myogenesis, Compartment A/B, Topologically associating domain, Differential chromatin interaction, Gene expression.
He M, Li Y, Tang Q, Li D, Jin L, Tian S, Che T, He S, Deng L, Gao G, Gu Y, Jiang Z, Li X, Li M. Genome-Wide Chromatin Structure Changes During Adipogenesis and Myogenesis. Int J Biol Sci 2018; 14(11):1571-1585. doi:10.7150/ijbs.25328. Available from http://www.ijbs.com/v14p1571.htm