Author/Authors :
Jennifer E. Phillips-Cremins، نويسنده , , Michael E.G. Sauria، نويسنده , , Amartya Sanyal، نويسنده , , Tatiana I. Gerasimova، نويسنده , , Bryan R. Lajoie، نويسنده , , Joshua S.K. Bell، نويسنده , , Chin-Tong Ong، نويسنده , , Tracy A. Hookway، نويسنده , , Changying Guo، نويسنده , , Yuhua Sun، نويسنده , , Michael J. Bland، نويسنده , , William Wagstaff، نويسنده , , Stephen Dalton، نويسنده , , Todd C. McDevitt، نويسنده , , Ranjan Sen، نويسنده , , Job Dekker، نويسنده , , James Taylor، نويسنده , , Victor G. Corces، نويسنده ,
Abstract :
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.
