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Genes 2016, 7(10), 71; doi:10.3390/genes7100071

Making Sense of the Tangle: Insights into Chromatin Folding and Gene Regulation

1
Department of Applied Bioscience, College of Life and Environmental Science, Konkuk University, Seoul 143 701, Korea
2
Department of Pathology, University of Otago, Dunedin 9016, New Zealand
3
Department of Biochemistry, Periyar University, Salem 636011, Tamil Nadu, India
*
Author to whom correspondence should be addressed.
Academic Editor: Paolo Cinelli
Received: 21 June 2016 / Revised: 10 August 2016 / Accepted: 7 September 2016 / Published: 23 September 2016
(This article belongs to the Section Molecular Genetics)
View Full-Text   |   Download PDF [1033 KB, uploaded 23 September 2016]   |  

Abstract

Proximity ligation assays such as circularized chromosome conformation capture and high-throughput chromosome capture assays have shed light on the structural organization of the interphase genome. Functional topologically associating domains (TADs) that constitute the building blocks of genomic organization are disrupted and reconstructed during the cell cycle. Epigenetic memory, as well as the sequence of chromosomes, regulate TAD reconstitution. Sub-TAD domains that are invariant across cell types have been identified, and contacts between these domains, rather than looping, are speculated to drive chromatin folding. Replication domains are established simultaneously with TADs during the cell cycle and the two correlate well in terms of characteristic features, such as lamin association and histone modifications. CCCTC-binding factor (CTCF) and cohesin cooperate across different cell types to regulate genes and genome organization. CTCF elements that demarcate TAD boundaries are commonly disrupted in cancer and promote oncogene activation. Chromatin looping facilitates interactions between distant promoters and enhancers, and the resulting enhanceosome complex promotes gene expression. Deciphering the chromatin tangle requires comprehensive integrative analyses of DNA- and protein-dependent factors that regulate genomic organization. View Full-Text
Keywords: chromatin folding; replication domains; topologically associating domains; gene regulation chromatin folding; replication domains; topologically associating domains; gene regulation
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Chung, I.-M.; Ketharnathan, S.; Kim, S.-H.; Thiruvengadam, M.; Rani, M.K.; Rajakumar, G. Making Sense of the Tangle: Insights into Chromatin Folding and Gene Regulation. Genes 2016, 7, 71.

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