Details

Autor(en) / Beteiligte

• 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.

Titel

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

Ist Teil von

• Cell, 2013-06, Vol.153 (6), p.1281-1295

Ort / Verlag

United States: Elsevier Inc

Erscheinungsjahr

2013

Quelle

MEDLINE

Beschreibungen/Notizen

• 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. [Display omitted] •Genome architecture is reorganized at the sub-Mb scale during differentiation•CTCF, Mediator, and cohesin have widespread and unique roles in genome organization•CTCF and cohesin anchor long-range, constitutive interactions•Mediator and cohesin bridge short-range, cell-type-specific interactions The differentiation of embryonic stem cells to neural progenitors is accompanied by submegabase changes in chromatin architecture. Distinct combinations of CTCF, Mediator and cohesin play specific roles in this chromatin reorganization, maintaining long-range interactions, while facilitating changes in short-range, promoter-enhancer contacts.