CTCF mediates long-range chromatin looping and local histone modification in the beta-globin locus.
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.
Splinter
Erik
E
Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
Heath
Helen
H
Kooren
Jurgen
J
Palstra
Robert-Jan
RJ
Klous
Petra
P
Grosveld
Frank
F
Galjart
Niels
N
de Laat
Wouter
W
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*
D000076246:CCCTC-Binding Factor; D002843:Chromatin; C000619698:Ctcf protein, mouse; D004268:DNA-Binding Proteins; D005819:Genetic Markers; D006657:Histones; D012097:Repressor Proteins; D005914:Globins