Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment
Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology
Chromatin; Nucleic Acid Conformation; Genome
Genetics and Genomics | Systems Biology
Understanding the topological configurations of chromatin may reveal valuable insights into how the genome and epigenome act in concert to control cell fate during development. Here, we generate high-resolution architecture maps across seven genomic loci in embryonic stem cells and neural progenitor cells. We observe a hierarchy of 3D interactions that undergo marked reorganization at the submegabase scale during differentiation. Distinct combinations of CCCTC-binding factor (CTCF), Mediator, and cohesin show widespread enrichment in chromatin interactions at different length scales. CTCF/cohesin anchor long-range constitutive interactions that might form the topological basis for invariant subdomains. Conversely, Mediator/cohesin bridge short-range enhancer-promoter interactions within and between larger subdomains. Knockdown of Smc1 or Med12 in embryonic stem cells results in disruption of spatial architecture and downregulation of genes found in cohesin-mediated interactions. We conclude that cell-type-specific chromatin organization occurs at the submegabase scale and that architectural proteins shape the genome in hierarchical length scales.
DOI of Published Version
Cell. 2013 Jun 6;153(6):1281-95. doi: 10.1016/j.cell.2013.04.053.
Phillips-Cremins JE, Sauria ME, Sanyal A, Gerasimova TI, Lajoie BR, Bell JS, Ong C, Hookway TA, Guo C, Sun Y, Bland MJ, Wagstaff W, Dalton S, McDevitt TC, Sen R, Dekker J, Taylor J, Corces VG. (2013). Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment. Program in Systems Biology Publications. https://doi.org/10.1016/j.cell.2013.04.053. Retrieved from https://escholarship.umassmed.edu/sysbio_pubs/27