About: Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection

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About: Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection Goto Sponge NotDistinct Permalink

An Entity of Type : schema:ScholarlyArticle, within Data Space : wasabi.inria.fr associated with source document(s)

Attributes	Values
type	Academic Article research paper schema:ScholarlyArticle
isDefinedBy	Covid-on-the-Web dataset
has title	Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
Creator	Li, Jingwei Guo, Ya Ge, Xiao Jia, Zhilian Wu, Qiang Wu, Yonghu
Source	Medline; PMC
abstract	BACKGROUND: CTCF is a key insulator-binding protein, and mammalian genomes contain numerous CTCF sites, many of which are organized in tandem. RESULTS: Using CRISPR DNA-fragment editing, in conjunction with chromosome conformation capture, we find that CTCF sites, if located between enhancers and promoters in the protocadherin (Pcdh) and β-globin clusters, function as an enhancer-blocking insulator by forming distinct directional chromatin loops, regardless whether enhancers contain CTCF sites or not. Moreover, computational simulation in silico and genetic deletions in vivo as well as dCas9 blocking in vitro revealed balanced promoter usage in cell populations and stochastic monoallelic expression in single cells by large arrays of tandem CTCF sites in the Pcdh and immunoglobulin heavy chain (Igh) clusters. Furthermore, CTCF insulators promote, counter-intuitively, long-range chromatin interactions with distal directional CTCF sites, consistent with the cohesin “loop extrusion” model. Finally, gene expression levels are negatively correlated with CTCF insulators located between enhancers and promoters on a genome-wide scale. Thus, single CTCF insulators ensure proper enhancer insulation and promoter activation while tandem CTCF topological insulators determine balanced spatial contacts and promoter choice. CONCLUSIONS: These findings have interesting implications on the role of topological chromatin insulators in 3D genome folding and developmental gene regulation.
has issue date	2020-03-23(xsd:dateTime)
bibo:doi	10.1186/s13059-020-01984-7
bibo:pmid	32293525
has license	cc-by
sha1sum (hex)	a02c9ea4d8034898c871804abe62183ad528d612
schema:url	https://doi.org/10.1186/s13059-020-01984-7
resource representing a document's title	Tandem CTCF sites function as insulators to balance spatial chromatin contacts and topological enhancer-promoter selection
has PubMed Central identifier	PMC7087399
has PubMed identifier	32293525
schema:publication	Genome Biol
resource representing a document's body	covid:a02c9ea4d8034898c871804abe62183ad528d612#body_text
is schema:about of	named entity 'ENHANCER' named entity 'extrusion' named entity 'chromosome conformation capture' named entity 'correlated' named entity 'CTCF' named entity 'sites' named entity 'β-globin' named entity 'protein' named entity 'heavy chain' named entity 'consistent' named entity 'CTCF' named entity 'immunoglobulin' named entity 'dCas9' named entity 'numerous' named entity 'spatial' named entity 'function' named entity 'SELECTION' named entity 'CONTACTS' named entity 'POPULATIONS' named entity 'COHESIN' named entity 'GENE EXPRESSION LEVELS' named entity 'GENOMES' named entity 'IMMUNOGLOBULIN HEAVY CHAIN' named entity 'CONTAIN' named entity 'TANDEM' named entity 'USAGE' named entity 'PROPER' named entity 'USING' named entity 'SINGLE' named entity 'IN VITRO' named entity 'FRAGMENT' named entity 'NUMEROUS' named entity 'CRISPR' named entity 'MAMMALIAN' named entity 'INTERACTIONS' named entity 'RESULTS' named entity 'KEY' named entity 'FUNCTION' named entity 'PROMOTER' named entity 'CHROMATIN' named entity 'INSULATORS' named entity 'CHROMATIN' named entity 'IN VIVO' named entity 'CHOICE' named entity 'CONTACTS' named entity 'REGARDLESS' named entity 'COMPUTATIONAL SIMULATION' named entity 'LOOPS' named entity 'EXPRESSION' named entity 'PROTOCADHERIN' named entity 'BLOCKING' named entity 'CLUSTERS' named entity 'GLOBIN' named entity 'CONJUNCTION' named entity 'GENOME' named entity 'GENETIC' named entity 'LONG' named entity 'DETERMINE' named entity 'PROMOTE' named entity 'INSULATOR' named entity 'INSULATORS' named entity 'SPATIAL' named entity 'ENSURE' named entity 'ORGANIZED' named entity 'WIDE' named entity 'FUNCTION' named entity 'IN SILICO' named entity 'TANDEM' named entity 'MODEL' named entity 'BACKGROUND' named entity 'PROMOTER' named entity 'EDITING' named entity 'SITES' named entity 'CELLS' named entity 'DISTAL' named entity 'RANGE'

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