Referenced in: none

Automatically associated channels: Kv7.5

Title: CTCF mediates the cell-type specific spatial organization of the Kcnq5 locus and the local gene regulation.

Authors: Licheng Ren, Yang Wang, Minglei Shi, Xiaoning Wang, Zhong Yang, Zhihu Zhao

Journal, date & volume: PLoS ONE, 2012 , 7, e31416

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/22347474

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.