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Comment
. 2015 May 21;161(5):955-957.
doi: 10.1016/j.cell.2015.04.047.

A CRISPR Connection between Chromatin Topology and Genetic Disorders

Bing Ren  1 , Jesse R Dixon  2
Affiliations
Comment

A CRISPR Connection between Chromatin Topology and Genetic Disorders

Bing Ren et al. Cell. .

Abstract

Structural variations are common in the human genome, but their contributions to human diseases have been hard to define. Lupiáñez et al. demonstrate that some structural variants can interrupt chromatin topology, resulting in ectopic enhancer-promoter interactions, altered spatiotemporal gene expression patterns, and developmental disorders.

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Figures

Figure 1
Figure 1. Structural variation and pathological rewiring of genetic regulatory interactions
A genetic locus that includes genes and enhancers relevant to mammalian limb formation (top) has undergone deletions and inversions in humans causing altered promoter-enhancer interactions (middle) and three distinct malformation syndromes (bottom). Recapitulating these structural variations in mice indicates that disruption of the TAD boundary domain is a key component of rewired circuitry and a pathological phenotype.
See this image and copyright information in PMC

Comment on

  • Disruptions of topological chromatin domains cause pathogenic rewiring of gene-enhancer interactions.
    Lupiáñez DG, Kraft K, Heinrich V, Krawitz P, Brancati F, Klopocki E, Horn D, Kayserili H, Opitz JM, Laxova R, Santos-Simarro F, Gilbert-Dussardier B, Wittler L, Borschiwer M, Haas SA, Osterwalder M, Franke M, Timmermann B, Hecht J, Spielmann M, Visel A, Mundlos S. Lupiáñez DG, et al. Cell. 2015 May 21;161(5):1012-1025. doi: 10.1016/j.cell.2015.04.004. Epub 2015 May 7. Cell. 2015. PMID: 25959774 Free PMC article.

References

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