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Cell. 2014 May 8;157(4):950-63. doi: 10.1016/j.cell.2014.03.025.

Predictive polymer modeling reveals coupled fluctuations in chromosome conformation and transcription.

Author information

1
Institut Curie, 26 Rue d'Ulm, 75248 Paris Cedex 05, France; CNRS UMR3215, 75248 Paris Cedex 05, France; INSERM U934, 75248 Paris Cedex 05, France.
2
Institut Curie, 26 Rue d'Ulm, 75248 Paris Cedex 05, France.
3
Program in Systems Biology, Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, 368 Plantation Street, Worcester, MA 01605-0103, USA.
4
Dipartimento di Fisica, Università degli Studi di Milano and INFN, Via Celoria 16, 20133 Milano, Italy. Electronic address: guido.tiana@unimi.it.
5
Institut Curie, 26 Rue d'Ulm, 75248 Paris Cedex 05, France; CNRS UMR3215, 75248 Paris Cedex 05, France; INSERM U934, 75248 Paris Cedex 05, France; Collège de France, 11 place Marcelin-Berthelot, Paris 75005, France. Electronic address: edith.heard@curie.fr.

Abstract

A new level of chromosome organization, topologically associating domains (TADs), was recently uncovered by chromosome conformation capture (3C) techniques. To explore TAD structure and function, we developed a polymer model that can extract the full repertoire of chromatin conformations within TADs from population-based 3C data. This model predicts actual physical distances and to what extent chromosomal contacts vary between cells. It also identifies interactions within single TADs that stabilize boundaries between TADs and allows us to identify and genetically validate key structural elements within TADs. Combining the model's predictions with high-resolution DNA FISH and quantitative RNA FISH for TADs within the X-inactivation center (Xic), we dissect the relationship between transcription and spatial proximity to cis-regulatory elements. We demonstrate that contacts between potential regulatory elements occur in the context of fluctuating structures rather than stable loops and propose that such fluctuations may contribute to asymmetric expression in the Xic during X inactivation.

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PMID:
24813616
PMCID:
PMC4427251
DOI:
10.1016/j.cell.2014.03.025
[Indexed for MEDLINE]
Free PMC Article

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