Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Review
. 2016 Dec;17(12):771-782.
doi: 10.1038/nrm.2016.138. Epub 2016 Nov 9.

Regulation of disease-associated gene expression in the 3D genome

Peter Hugo Lodewijk Krijger  1 , Wouter de Laat  1
Affiliations
Review

Regulation of disease-associated gene expression in the 3D genome

Peter Hugo Lodewijk Krijger et al. Nat Rev Mol Cell Biol. 2016 Dec.

Abstract

Genetic variation associated with disease often appears in non-coding parts of the genome. Understanding the mechanisms by which this phenomenon leads to disease is necessary to translate results from genetic association studies to the clinic. Assigning function to this type of variation is notoriously difficult because the human genome harbours a complex regulatory landscape with a dizzying array of transcriptional regulatory sequences, such as enhancers that have unpredictable, promiscuous and context-dependent behaviour. In this Review, we discuss how technological advances have provided increasingly detailed information on genome folding; for example, genome folding forms loops that bring enhancers and target genes into close proximity. We also now know that enhancers function within topologically associated domains, which are structural and functional units of chromosomes. Studying disease-associated mutations and chromosomal rearrangements in the context of the 3D genome will enable the identification of dysregulated target genes and aid the progression from descriptive genetic association results to discovering molecular mechanisms underlying disease.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

References

    1. Mol Cell. 2015 Nov 19;60(4):676-84 - PubMed
    1. Cell Stem Cell. 2016 May 5;18(5):611-24 - PubMed
    1. N Engl J Med. 2015 Sep 3;373(10 ):895-907 - PubMed
    1. Cell Rep. 2016 May 31;15(9):2038-49 - PubMed
    1. Cell. 2013 Nov 7;155(4):934-47 - PubMed

LinkOut - more resources