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Canonical and single-cell Hi-C reveal distinct chromatin interaction sub-networks of mammalian transcription factors.

cam.issuedOnline2018-10-25
dc.contributor.authorMa, Xiaoyan
dc.contributor.authorEzer, Daphne
dc.contributor.authorAdryan, Boris
dc.contributor.authorStevens, Tim J
dc.contributor.orcidStevens, Tim J [0000-0001-6475-2074]
dc.date.accessioned2018-10-26T10:58:44Z
dc.date.available2018-10-26T10:58:44Z
dc.date.issued2018-10-25
dc.date.updated2018-10-26T10:58:42Z
dc.description.abstractBACKGROUND: Transcription factor (TF) binding to regulatory DNA sites is a key determinant of cell identity within multi-cellular organisms and has been studied extensively in relation to site affinity and chromatin modifications. There has been a strong focus on the inference of TF-gene regulatory networks and TF-TF physical interaction networks. Here, we present a third type of TF network, the spatial network of co-localized TF binding sites within the three-dimensional genome. RESULTS: Using published canonical Hi-C data and single-cell genome structures, we assess the spatial proximity of a genome-wide array of potential TF-TF co-localizations in human and mouse cell lines. For individual TFs, the abundance of occupied binding sites shows a positive correspondence with their clustering in three dimensions, and this is especially apparent for weak TF binding sites and at enhancer regions. An analysis between different TF proteins identifies significantly proximal pairs, which are enriched in reported physical interactions. Furthermore, clustering of different TFs based on proximity enrichment identifies two partially segregated co-localization sub-networks, involving different TFs in different cell types. Using data from both human lymphoblastoid cells and mouse embryonic stem cells, we find that these sub-networks are enriched within, but not exclusive to, different chromosome sub-compartments that have been identified previously in Hi-C data. CONCLUSIONS: This suggests that the association of TFs within spatial networks is closely coupled to gene regulatory networks. This applies to both differentiated and undifferentiated cells and is a potential causal link between lineage-specific TF binding and chromosome sub-compartment segregation.
dc.identifier.citationGenome Biology. 2018 Oct 25;19(1):174
dc.identifier.doi10.17863/CAM.31772
dc.identifier.eissn1474-760X
dc.identifier.issn1474-7596
dc.identifier.urihttps://www.repository.cam.ac.uk/handle/1810/284396
dc.language.isoeng
dc.language.rfc3066en
dc.publisherSpringer Science and Business Media LLC
dc.publisher.urlhttp://dx.doi.org/10.1186/s13059-018-1558-2
dc.rights.holderThe Author(s).
dc.subjectChromatin conformational capture
dc.subjectChromosome compartment
dc.subjectGenome structure
dc.subjectHi-C
dc.subjectNuclear organization
dc.subjectProximity network
dc.subjectTranscription factor
dc.subjectAnimals
dc.subjectBinding Sites
dc.subjectCell Line
dc.subjectChromatin
dc.subjectGene Regulatory Networks
dc.subjectGenes, Reporter
dc.subjectGenome
dc.subjectHumans
dc.subjectLymphocytes
dc.subjectMammals
dc.subjectMice
dc.subjectOrgan Specificity
dc.subjectTranscription Factors
dc.titleCanonical and single-cell Hi-C reveal distinct chromatin interaction sub-networks of mammalian transcription factors.
dc.typeJournal Article
dcterms.dateAccepted2018-10-04
prism.publicationNameGenome Biol
rioxxterms.versionofrecord10.1186/s13059-018-1558-2

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