Architectural Protein Subclasses Shape 3D Organization of Genomes during Lineage Commitment
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Authors
Phillips-Cremins, Jennifer E.Sauria, Michael E. G.
Sanyal, Amartya
Gerasimova, Tatiana I.
Lajoie, Bryan R.
Bell, Joshua S. K.
Ong, Chin-Tong
Hookway, Tracy A.
Guo, Changying
Sun, Yuhua
Bland, Michael J.
Wagstaff, William
Dalton, Stephen
McDevitt, Todd C.
Sen, Ranjan
Dekker, Job
Taylor, James
Corces, Victor G.
UMass Chan Affiliations
Department of Biochemistry and Molecular PharmacologyProgram in Systems Biology
Document Type
Journal ArticlePublication Date
2013-06-06
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Show full item recordAbstract
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.Source
Cell. 2013 Jun 6;153(6):1281-95. doi: 10.1016/j.cell.2013.04.053.DOI
10.1016/j.cell.2013.04.053Permanent Link to this Item
http://hdl.handle.net/20.500.14038/49909PubMed ID
23706625Related Resources
Link to article in PubMedae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2013.04.053