ctcf mediates the cell-type specific spatial organization of the kcnq5 locus and the local gene regulationctcf介导特异性kcnq5轨迹的空间组织和当地的基因调控.pdfVIP

CTCF Mediates the Cell-Type Specific Spatial Organization of the Kcnq5 Locus and the Local Gene Regulation 1¤ 2 2 1,3 1,3 2 Licheng Ren , Yang Wang , Minglei Shi , Xiaoning Wang *, Zhong Yang *, Zhihu Zhao * 1 State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai, China, 2 Beijing Institute of Biotechnology, Fengtai District, Beijing, China, 3 State Key Laboratory of Genetic Engineering and Department of Microbiology and Microbial Engineering, School of Life Sciences, Fudan University, Shanghai, China 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 luc