Title | Architectural protein subclasses shape 3D organization of genomes during lineage commitment. |
Publication Type | Journal Article |
Year of Publication | 2013 |
Authors | Phillips-Cremins, JE, Sauria, MEG, Sanyal, A, Gerasimova, TI, Lajoie, BR, Bell, JSK, Ong, C-T, Hookway, TA, Guo, C, Sun, Y, Bland, MJ, Wagstaff, W, Dalton, S, McDevitt, TC, Sen, R, Dekker, J, Taylor, J, Corces, VG |
Journal | Cell |
Date Published | June 2013 |
ISSN | 1097-4172 |
Keywords | Animals, Cell Cycle Proteins, Cell Lineage, Chromatin, Chromosomal Proteins, Non-Histone, Embryonic Stem Cells, Enhancer Elements, Genetic, Gene Expression Regulation, Developmental, Gene Knockdown Techniques, Genome, Genome-Wide Association Study, Mediator Complex, Mice, Neural Stem Cells, Nuclear Proteins, Promoter Regions, Genetic, Repressor Proteins, Sequence Analysis, DNA |
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. |
DOI | 10.1016/j.cell.2013.04.053 |
Alternate Journal | Cell |
PubMed ID | 23706625 |
PubMed Central ID | PMC3712340 |
Grant List | RC2HG005542 / HG / NHGRI NIH HHS / United States R01HG003143 / HG / NHGRI NIH HHS / United States R01GM035463 / GM / NIGMS NIH HHS / United States R01DK065806 / DK / NIDDK NIH HHS / United States R01 HG003143 / HG / NHGRI NIH HHS / United States R01 GM035463 / GM / NIGMS NIH HHS / United States P01GM85354 / GM / NIGMS NIH HHS / United States 5F32NS065603 / NS / NINDS NIH HHS / United States T32 GM008490 / GM / NIGMS NIH HHS / United States |