Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control
Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occu...
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| Format: | Article |
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Elsevier
2018
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| Online Access: | http://hdl.handle.net/1721.1/116984 https://orcid.org/0000-0001-8855-8647 |
| _version_ | 1826191228398469120 |
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| author | Hnisz, Denes Day, Daniel S. Young, Richard A. |
| author2 | Massachusetts Institute of Technology. Department of Biology |
| author_facet | Massachusetts Institute of Technology. Department of Biology Hnisz, Denes Day, Daniel S. Young, Richard A. |
| author_sort | Hnisz, Denes |
| collection | MIT |
| description | Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease. Insulated neighborhoods are a powerful paradigm for gene control that provides new insights into development and disease. |
| first_indexed | 2024-09-23T08:52:58Z |
| format | Article |
| id | mit-1721.1/116984 |
| institution | Massachusetts Institute of Technology |
| last_indexed | 2024-09-23T08:52:58Z |
| publishDate | 2018 |
| publisher | Elsevier |
| record_format | dspace |
| spelling | mit-1721.1/1169842022-09-30T11:53:29Z Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control Hnisz, Denes Day, Daniel S. Young, Richard A. Massachusetts Institute of Technology. Department of Biology Young, Richard A Understanding how transcriptional enhancers control over 20,000 protein-coding genes to maintain cell-type-specific gene expression programs in all human cells is a fundamental challenge in regulatory biology. Recent studies suggest that gene regulatory elements and their target genes generally occur within insulated neighborhoods, which are chromosomal loop structures formed by the interaction of two DNA sites bound by the CTCF protein and occupied by the cohesin complex. Here, we review evidence that insulated neighborhoods provide for specific enhancer-gene interactions, are essential for both normal gene activation and repression, form a chromosome scaffold that is largely preserved throughout development, and are perturbed by genetic and epigenetic factors in disease. Insulated neighborhoods are a powerful paradigm for gene control that provides new insights into development and disease. National Institutes of Health (U.S.) (Grant HG002668) 2018-07-13T17:55:38Z 2018-07-13T17:55:38Z 2016-11 2018-07-13T17:32:29Z Article http://purl.org/eprint/type/JournalArticle 0092-8674 1097-4172 http://hdl.handle.net/1721.1/116984 Hnisz, Denes et al. “Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control.” Cell 167, 5 (November 2016): 1188–1200 © 2016 Elsevier Inc https://orcid.org/0000-0001-8855-8647 http://dx.doi.org/10.1016/J.CELL.2016.10.024 Cell Creative Commons Attribution-NonCommercial-NoDerivs License http://creativecommons.org/licenses/by-nc-nd/4.0/ application/pdf Elsevier PMC |
| spellingShingle | Hnisz, Denes Day, Daniel S. Young, Richard A. Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title | Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title_full | Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title_fullStr | Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title_full_unstemmed | Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title_short | Insulated Neighborhoods: Structural and Functional Units of Mammalian Gene Control |
| title_sort | insulated neighborhoods structural and functional units of mammalian gene control |
| url | http://hdl.handle.net/1721.1/116984 https://orcid.org/0000-0001-8855-8647 |
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