title: CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus.
abstract: CTCF (CCCTC-binding factor) binds sites around the mouse beta-globin locus that spatially cluster in the erythroid cell nucleus. We show that both conditional deletion of CTCF and targeted disruption of a DNA-binding site destabilize these long-range interactions and cause local loss of histone acetylation and gain of histone methylation, apparently without affecting transcription at the locus. Our data demonstrate that CTCF is directly involved in chromatin architecture and regulates local balance between active and repressive chromatin marks. We postulate that throughout the genome, relative position and stability of CTCF-mediated loops determine their effect on enhancer-promoter interactions, with gene insulation as one possible outcome.
authors.affiliation: Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
authors.forename: Erik
authors.initials: E
authors.lastname: Splinter
authors.forename: Helen
authors.initials: H
authors.lastname: Heath
authors.forename: Jurgen
authors.initials: J
authors.lastname: Kooren
authors.forename: Robert-Jan
authors.initials: RJ
authors.lastname: Palstra
authors.forename: Petra
authors.initials: P
authors.lastname: Klous
authors.forename: Frank
authors.initials: F
authors.lastname: Grosveld
authors.forename: Niels
authors.initials: N
authors.lastname: Galjart
authors.forename: Wouter
authors.initials: W
authors.lastname: de Laat
mesh_terms: D000818:Animals; D000076246:CCCTC-Binding Factor; D002460:Cell Line; D002478:Cells, Cultured; D002843:Chromatin / Q000737:chemistry / Q000378:metabolism*; D004268:DNA-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000502:physiology*; D041905:Erythroid Cells / Q000378:metabolism; D005333:Fetus; D005819:Genetic Markers; D005914:Globins / Q000096:biosynthesis / Q000235:genetics* / Q000378:metabolism; D006657:Histones / Q000378:metabolism*; D051379:Mice; D018345:Mice, Knockout; D012097:Repressor Proteins / Q000235:genetics / Q000502:physiology*
chemical_list: D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006657:Histones; D012097:Repressor Proteins; D005914:Globins