title: CTCF mediates the cell-type specific spatial organization of the Kcnq5 locus and the local gene regulation.
abstract: Chromatin loops play important roles in the dynamic spatial organization of genes in the nucleus. Growing evidence has revealed that the multivalent functional zinc finger protein CCCTC-binding factor (CTCF) is a master regulator of genome spatial organization, and mediates the ubiquitous chromatin loops within the genome. Using circular chromosome conformation capture (4C) methodology, we discovered that CTCF may be a master organizer in mediating the spatial organization of the kcnq5 gene locus. We characterized the cell-type specific spatial organization of the kcnq5 gene locus mediated by CTCF in detail using chromosome conformation capture (3C) and 3C-derived techniques. Cohesion also participated in mediating the organization of this locus. RNAi-mediated knockdown of CTCF sharply diminished the interaction frequencies between the chromatin loops of the kcnq5 gene locus and down-regulated local gene expression. Functional analysis showed that the interacting chromatin loops of the kcnq5 gene locus can repress the gene expression in a luciferase reporter assay. These interacting chromatin fragments were a series of repressing elements whose contacts were mediated by CTCF. Therefore, these findings suggested that the dynamical spatial organization of the kcnq5 locus regulates local gene expression.
authors.affiliation: State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China.
authors.forename: Licheng
authors.initials: L
authors.lastname: Ren
authors.forename: Yang
authors.initials: Y
authors.lastname: Wang
authors.forename: Minglei
authors.initials: M
authors.lastname: Shi
authors.forename: Xiaoning
authors.initials: X
authors.lastname: Wang
authors.forename: Zhong
authors.initials: Z
authors.lastname: Yang
authors.forename: Zhihu
authors.initials: Z
authors.lastname: Zhao
mesh_terms: D000076246:CCCTC-Binding Factor; D045744:Cell Line, Tumor; D002843:Chromatin; D002875:Chromosomes; D005786:Gene Expression Regulation; D056426:Genetic Loci; D015894:Genome, Human; D006801:Humans; D051656:KCNQ Potassium Channels / Q000378:metabolism*; D012097:Repressor Proteins / Q000502:physiology*
chemical_list: D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D002843:Chromatin; D051656:KCNQ Potassium Channels; C412231:KCNQ5 protein, human; D012097:Repressor Proteins