Breaking TADs: How Alterations of Chromatin Domains Result in Disease

Darío G Lupiáñez; Malte Spielmann; Stefan Mundlos

doi:10.1016/j.tig.2016.01.003

Breaking TADs: How Alterations of Chromatin Domains Result in Disease

Trends Genet. 2016 Apr;32(4):225-237. doi: 10.1016/j.tig.2016.01.003. Epub 2016 Feb 7.

Authors

Darío G Lupiáñez¹, Malte Spielmann¹, Stefan Mundlos²

Affiliations

¹ Max Planck Institute for Molecular Genetics, RG Development and Disease, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany.
² Max Planck Institute for Molecular Genetics, RG Development and Disease, 14195 Berlin, Germany; Institute for Medical and Human Genetics, Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany; Berlin-Brandenburg Center for Regenerative Therapies (BCRT), Charité - Universitätsmedizin Berlin, 13353 Berlin, Germany. Electronic address: [email protected].

PMID: 26862051
DOI: 10.1016/j.tig.2016.01.003

Abstract

Spatial organization is an inherent property of the vertebrate genome to accommodate the roughly 2m of DNA in the nucleus of a cell. In this nonrandom organization, topologically associating domains (TADs) emerge as a fundamental structural unit that is thought to guide regulatory elements to their cognate promoters. In this review we summarize the most recent findings about TADs and the boundary regions separating them. We discuss how the disruption of these structures by genomic rearrangements can result in gene misexpression and disease.

Keywords: CRISPR/Cas; TAD; disease; long-range regulation; structural variations; topologically associating domains.

Publication types

Research Support, Non-U.S. Gov't
Review

MeSH terms

Chromatin / chemistry*
Chromatin / genetics
Genetic Predisposition to Disease*
Humans

Substances

Chromatin