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J Mol Biol. 2019 Nov 2. pii: S0022-2836(19)30610-2. doi: 10.1016/j.jmb.2019.10.014. [Epub ahead of print]

Higher-order chromosomal structures mediate genome function.

Author information

1
Institute of Human Genetics, CNRS and University of Montpellier, France.
2
Institute of Human Genetics, CNRS and University of Montpellier, France. Electronic address: frederic.bantignies@igh.cnrs.fr.
3
Institute of Human Genetics, CNRS and University of Montpellier, France. Electronic address: giacomo.cavalli@igh.cnrs.fr.

Abstract

How chromosomes are organized within the tridimensional space of the nucleus and how can this organization affect genome function have been long-standing questions on the path to understanding genome activity and its link to diseases. In the last decade, high-throughput chromosome conformation capture techniques, such as Hi-C, have facilitated the discovery of new principles of genome folding. Chromosomes are folded in multiple high-order structures, with local contacts between enhancers and promoters, intermediate-level contacts forming Topologically Associating Domains (TADs) and higher-order chromatin structures sequestering chromatin into active and repressive compartments. However, despite the increasing evidence that genome organization can influence its function, we are still far from understanding the underlying mechanisms. Deciphering these mechanisms represents a major challenge for the future, for which large, international initiatives, such as 4DN, HCA and LifeTime aim to collaboratively tackle by using a conjunction of state-of -the-art population-based and single-cell approaches.

PMID:
31689436
DOI:
10.1016/j.jmb.2019.10.014

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