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.
MeSH Terms
Animals
CCCTC-Binding Factor
Cell Line
Cells, Cultured
Chromatin/chemistry,metabolism
DNA-Binding Proteins/deficiency,genetics,physiology
Erythroid Cells/metabolism
Fetus
Genetic Markers
Globins/biosynthesis,genetics,metabolism
Histones/metabolism
Mice
Mice, Knockout
Repressor Proteins/genetics,physiology
Chemicals
CCCTC-Binding Factor
Chromatin
Ctcf protein, mouse
DNA-Binding Proteins
Genetic Markers
Histones
Repressor Proteins
Globins
Authors & Affiliations
8 authors, click to expand affiliations / ORCID
Splinter Erik
Department of Cell Biology and Genetics, Erasmus Medical Center, 3000 DR Rotterdam, The Netherlands.
Heath Helen
Kooren Jurgen
Palstra Robert-Jan
Klous Petra
Grosveld Frank
Galjart Niels
de Laat Wouter
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