Title

Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment

UMMS Affiliation

Program in Systems Biology; Department of Biochemistry and Molecular Pharmacology

Date

6-6-2013

Document Type

Article

Medical Subject Headings

Chromatin; Nucleic Acid Conformation; Genome

Disciplines

Genetics and Genomics | Systems Biology

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.

Rights and Permissions

Citation: Cell. 2013 Jun 6;153(6):1281-95. doi: 10.1016/j.cell.2013.04.053.

Related Resources

Link to article in PubMed

Journal Title

Cell

PubMed ID

23706625