Cell type specificity of chromatin organization mediated by CTCF and cohesin.
CTCF sites are abundant in the genomes of diverse species but their function is enigmatic. We used chromosome conformation capture to determine long-range interactions among CTCF/cohesin sites over 2 Mb on human chromosome 11 encompassing the beta-globin locus and flanking olfactory receptor genes. Although CTCF occupies these sites in both erythroid K562 cells and fibroblast 293T cells, the long-range interaction frequencies among the sites are highly cell type specific, revealing a more densely clustered organization in the absence of globin gene activity. Both CTCF and cohesins are required for the cell-type-specific chromatin conformation. Furthermore, loss of the organizational loops in K562 cells through reduction of CTCF with shRNA results in acquisition of repressive histone marks in the globin locus and reduces globin gene expression whereas silent flanking olfactory receptor genes are unaffected. These results support a genome-wide role for CTCF/cohesin sites through loop formation that both influences transcription and contributes to cell-type-specific chromatin organization and function.
Laboratory of Cellular and Developmental Biology, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, MD 20892, USA.
Chunhui
C
Hou
Ryan
R
Dale
Ann
A
Dean
D001665:Binding Sites; D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins / Q000378:metabolism*; D002460:Cell Line; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism* / Q000648:ultrastructure; D047369:Chromatin Immunoprecipitation; D002868:Chromosomal Proteins, Non-Histone / Q000378:metabolism*; D002880:Chromosomes, Human, Pair 11 / Q000235:genetics / Q000378:metabolism*; D005786:Gene Expression Regulation; D056426:Genetic Loci; D006801:Humans; D038101:Insulator Elements; D011487:Protein Conformation; D018035:Receptors, Odorant / Q000235:genetics; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D055544:beta-Globins / Q000235:genetics; D000097722:Cohesins
D000076246:CCCTC-Binding Factor; D018797:Cell Cycle Proteins; D002843:Chromatin; D002868:Chromosomal Proteins, Non-Histone; D018035:Receptors, Odorant; D012097:Repressor Proteins; D055544:beta-Globins; D000097722:Cohesins; C000619697:CTCF protein, human