Open AccessHierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation
Author(s) -
Fraser James,
Ferrai Carmelo,
Chiariello Andrea M,
Schueler Markus,
Rito Tiago,
Laudanno Giovanni,
Barbieri Mariano,
Moore Benjamin L,
Kraemer Dorothee CA,
Aitken Stuart,
Xie Sheila Q,
Morris Kelly J,
Itoh Masayoshi,
Kawaji Hideya,
Jaeger Ines,
Hayashizaki Yoshihide,
Carninci Piero,
Forrest Alistair RR,
Semple Colin A,
Dostie Josée,
Pombo Ana,
Nicodemi Mario
Publication year - 2015
Publication title -
molecular systems biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 8.523
H-Index - 148
ISSN - 1744-4292
DOI - 10.15252/msb.20156492
Subject(s) - biology , computational biology , genetics , microbiology and biotechnology , folding (dsp implementation) , evolutionary biology , electrical engineering , engineering
Mammalian chromosomes fold into arrays of megabase‐sized topologically associating domains ( TAD s), which are arranged into compartments spanning multiple megabases of genomic DNA . TAD s 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 (meta TAD s) 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. meta TAD 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.