학술논문
Hierarchical folding and reorganization of chromosomes are linked to transcriptional changes in cellular differentiation.
Document Type
Article
Author
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
Source
Subject
*CHROMATIN
*CHROMOSOMES
*EPIGENETICS
*GENE expression
*POLYMERS
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Language
ISSN
1744-4292
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 (meta TADs) 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. [ABSTRACT FROM AUTHOR]