Breaking TADs: How Alterations of Chromatin Domains Result in Disease
Open accessAbstract
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.
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Disruption of TADs can cause promiscuous enhancer-promoter contacts and ectopic gene expression leading to developmental aberrations and disease.
“disruption of TADs can cause promiscuous enhancer–promoter contacts and ectopic gene expression leading to developmental aberrations and disease (reviewed in [445])”
From Transcriptional enhancers and their communication with gene promoters (2021) · cites this paper as [445]
In “TADs and Disease,” the review reports that disrupted TAD boundaries permit ectopic enhancer–promoter interactions and gene misexpression that cause malformations. But “Additional information” cautions that enhancers are not simply promiscuous or nonselective: only a subset of accessible genes responds. The claim is supported except for that characterization of the contacts. (LLM, conf=0.87)
Experimental — accuracy not yet measuredTADs appear to restrict the areas of enhancer action.
“Second, it was demonstrated that eukaryotic chromosomes are partitioned into so-called topologically associated domains (TADs) [35,36,37], which appear to restrict the areas of enhancer action [38,39,40,41].”
From Enhancer Function in the 3D Genome (2023) · cites this paper as [40]
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References 96 · Cited by 439
Research works printed but not linked: 7
- Nora, E.P. et al. (2013) Segmental folding of chromosomes: a basis for structural and regulatory chromosomal neighborhoods? Bioessays 35, 818-828 Trends in Genetics, April 2016, Vol. 32, No. 4 235
- Hou, C. et al. (2010) Cell type specificity of chromatin organization mediated by CTCF and cohesin. Proc. Natl. Acad. Sci. U.S.A. 107, 3651-3656
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- Authors
- Lupiáñez, D. G., Spielmann, M., & Mundlos, S.
- Affiliations
- Berlin-Brandenburger Centrum für Regenerative Therapien (DE)
- Corresponding author
- Mundlos, Stefan
- Venue
- Trends in Genetics
- Publisher
- Elsevier BV
- Published
- 2016-04
- Volume
- 32
- Issue
- 4
- Pages
- 225-237
- ISSN
- 0168-9525 (ISSN-L)
- OpenAlex
- W2267070684
- Cited by
- 439
- References
- 96
- Citations by year
- 2026: 16 · 2025: 24 · 2024: 34 · 2023: 30 · 2022: 48 · 2021: 61 · 2020: 54 · 2019: 59 · 2018: 48 · 2017: 42 · 2016: 19 · 2014: 1
- FWCI
- 5.06
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Trends in Genetics (publishedVersion)
- PubMed (publishedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
- Funders
- Max-Planck-Förderstiftung
- Deutsche Forschungsgemeinschaft
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Nuclear Structure and Function
- Keywords
- topologically associating domains, chromatin domains, 3D genome organization, genome rearrangement, gene misexpression, chromatin looping, disease
- MeSH terms
- Chromatin, Humans, Genetic Predisposition to Disease
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