Architectural protein subclasses shape 3D organization of genomes during lineage commitment

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

doi:10.1016/j.cell.2013.04.053

Architectural protein subclasses shape 3D organization of genomes during lineage commitment

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

Research output: Contribution to journal › Article › peer-review

699 Scopus citations

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.

Original language	English (US)
Pages (from-to)	1281-1295
Number of pages	15
Journal	Cell
Volume	153
Issue number	6
DOIs	https://doi.org/10.1016/j.cell.2013.04.053
State	Published - Jun 6 2013
Externally published	Yes

ASJC Scopus subject areas

Biochemistry, Genetics and Molecular Biology(all)

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Phillips-Cremins, J. E., Sauria, M. E. G., Sanyal, A., Gerasimova, T. I., Lajoie, B. R., Bell, J. S. K., Ong, C. T., Hookway, T. A., Guo, C., Sun, Y., Bland, M. J., Wagstaff, W., Dalton, S., McDevitt, T. C., Sen, R., Dekker, J., Taylor, J., & Corces, V. G. (2013). Architectural protein subclasses shape 3D organization of genomes during lineage commitment. Cell, 153(6), 1281-1295. https://doi.org/10.1016/j.cell.2013.04.053

Phillips-Cremins, JE, Sauria, MEG, Sanyal, A, Gerasimova, TI, Lajoie, BR, Bell, JSK, Ong, CT, Hookway, TA, Guo, C, Sun, Y, Bland, MJ, Wagstaff, W, Dalton, S, McDevitt, TC, Sen, R, Dekker, J, Taylor, J & Corces, VG 2013, 'Architectural protein subclasses shape 3D organization of genomes during lineage commitment', Cell, vol. 153, no. 6, pp. 1281-1295. https://doi.org/10.1016/j.cell.2013.04.053

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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.",

author = "Phillips-Cremins, {Jennifer E.} and Sauria, {Michael E G} and Amartya Sanyal and Gerasimova, {Tatiana I.} and Lajoie, {Bryan R.} and Bell, {Joshua S K} and Ong, {Chin Tong} and Hookway, {Tracy A.} and Changying Guo and Yuhua Sun and Bland, {Michael J.} and William Wagstaff and Stephen Dalton and McDevitt, {Todd C.} and Ranjan Sen and Job Dekker and James Taylor and Corces, {Victor G.}",

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AU - Sauria, Michael E G

AU - Sanyal, Amartya

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AU - Lajoie, Bryan R.

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AU - Ong, Chin Tong

AU - Hookway, Tracy A.

AU - Guo, Changying

AU - Sun, Yuhua

AU - Bland, Michael J.

AU - Wagstaff, William

AU - Dalton, Stephen

AU - McDevitt, Todd C.

AU - Sen, Ranjan

AU - Dekker, Job

AU - Taylor, James

AU - Corces, Victor G.

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N2 - 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.

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Architectural protein subclasses shape 3D organization of genomes during lineage commitment

Abstract

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