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Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation

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Item Type:Article
Title:Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation
Creators Name:Fraser, J. and Ferrai, C. and Chiariello, A.M. and Schueler, M. and Rito, T. and Laudanno, G. and Barbieri, M. and Moore, B.L. and Kraemer, D.C.A. and Aitken, S. and Xie, S.Q. and Morris, K.J. and Itoh, M. and Kawaji, H. and Jaeger, I. and Hayashizaki, Y. and Carninci, P. and Forrest, A.R.R. and Semple, C.A. and Dostie, J. and Pombo, A. and Nicodemi, M.
Abstract:Mammalian chromosomes fold into arrays of megabase-sized topologically associating domains (TADs), which are arranged into compartments spanning multiple megabases of genomic DNA. TADs have internal substructures that are often cell type specific, but their higher-order organization remains elusive. Here, we investigate TAD higher-order interactions with Hi-C through neuronal differentiation and show that they form a hierarchy of domains-within-domains (metaTADs) extending across genomic scales up to the range of entire chromosomes. We find that TAD interactions are well captured by tree-like, hierarchical structures irrespective of cell type. metaTAD tree structures correlate with genetic, epigenomic and expression features, and structural tree rearrangements during differentiation are linked to transcriptional state changes. Using polymer modelling, we demonstrate that hierarchical folding promotes efficient chromatin packaging without the loss of contact specificity, highlighting a role far beyond the simple need for packing efficiency.
Keywords:Chromatin Contacts, Chromosome Architecture, Epigenetics, Gene Expression, Polymer Modelling, Animals, Mice
Source:Molecular Systems Biology
ISSN:1744-4292
Publisher:EMBO Press
Volume:11
Number:12
Page Range:852
Date:23 December 2015
Official Publication:https://doi.org/10.15252/msb.20156492
PubMed:View item in PubMed

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