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dc.contributor.authorPoterlowicz, Krzysztof
dc.contributor.authorYarker, Joanne L.
dc.contributor.authorMalashchuk, Igor
dc.contributor.authorLajoie, B.R.
dc.contributor.authorMardaryev, Andrei N.
dc.contributor.authorGdula, M.R.
dc.contributor.authorSharov, A.A.
dc.contributor.authorKohwi-Shigematsu, T.
dc.contributor.authorBotchkarev, Vladimir A.
dc.contributor.authorFessing, Michael Y.
dc.date.accessioned2020-07-15T13:15:50Z
dc.date.available2020-07-15T13:15:50Z
dc.date.issued2017
dc.identifier.citationPoterlowicz K, Yarker JL, Malashchuk I et al (2017) 5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cells. PLoS Genetics. 13(9): e1006966.en_US
dc.identifier.urihttp://hdl.handle.net/10454/17918
dc.descriptionYesen_US
dc.description.abstractMammalian genomes contain several dozens of large (>0.5 Mbp) lineage-specific gene loci harbouring functionally related genes. However, spatial chromatin folding, organization of the enhancer-promoter networks and their relevance to Topologically Associating Domains (TADs) in these loci remain poorly understood. TADs are principle units of the genome folding and represents the DNA regions within which DNA interacts more frequently and less frequently across the TAD boundary. Here, we used Chromatin Conformation Capture Carbon Copy (5C) technology to characterize spatial chromatin interaction network in the 3.1 Mb Epidermal Differentiation Complex (EDC) locus harbouring 61 functionally related genes that show lineage-specific activation during terminal keratinocyte differentiation in the epidermis. 5C data validated by 3D-FISH demonstrate that the EDC locus is organized into several TADs showing distinct lineage-specific chromatin interaction networks based on their transcription activity and the gene-rich or gene-poor status. Correlation of the 5C results with genome-wide studies for enhancer-specific histone modifications (H3K4me1 and H3K27ac) revealed that the majority of spatial chromatin interactions that involves the gene-rich TADs at the EDC locus in keratinocytes include both intra- and inter-TAD interaction networks, connecting gene promoters and enhancers. Compared to thymocytes in which the EDC locus is mostly transcriptionally inactive, these interactions were found to be keratinocyte-specific. In keratinocytes, the promoter-enhancer anchoring regions in the gene-rich transcriptionally active TADs are enriched for the binding of chromatin architectural proteins CTCF, Rad21 and chromatin remodeler Brg1. In contrast to gene-rich TADs, gene-poor TADs show preferential spatial contacts with each other, do not contain active enhancers and show decreased binding of CTCF, Rad21 and Brg1 in keratinocytes. Thus, spatial interactions between gene promoters and enhancers at the multi-TAD EDC locus in skin epithelial cells are cell type-specific and involve extensive contacts within TADs as well as between different gene-rich TADs, forming the framework for lineage-specific transcription.en_US
dc.description.sponsorshipThis study was supported by the grants 5R01AR064580 and 1RO1AR071727 to VAB, TKS and AAS, as well as by the grants from MRC (MR/ M010015/1) and BBSRC (BB/K010050/1) to VAB.en_US
dc.language.isoenen_US
dc.relation.isreferencedbyhttps://doi.org/10.1371/journal.pgen.1006966en_US
dc.rights© 2017 Poterlowicz et al. This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectEpidermal Differentiation Complex (EDC)en_US
dc.subject5C analysisen_US
dc.subjectTopologically Associating Domains (TADs)en_US
dc.subjectGene activityen_US
dc.subjectSpatial contact networken_US
dc.title5C analysis of the Epidermal Differentiation Complex locus reveals distinct chromatin interaction networks between gene-rich and gene-poor TADs in skin epithelial cellsen_US
dc.status.refereedYesen_US
dc.date.Accepted2017-08-08
dc.date.application2017-09-01
dc.typeArticleen_US
dc.type.versionPublished versionen_US
refterms.dateFOA2020-07-15T13:15:51Z


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