CTCF mediates long-range chromatin looping and local histone modification in the β-globin locus
- Erik Splinter1,
- Helen Heath1,
- Jurgen Kooren,
- Robert-Jan Palstra,
- Petra Klous,
- Frank Grosveld,
- Niels Galjart, and
- Wouter de Laat2
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↵1 These authors contributed equally to this work.
Abstract
CTCF (CCCTC-binding factor) binds sites around the mouse β-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.
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Footnotes
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↵2 Corresponding author.
↵2 E-MAIL w.delaat{at}erasmusmc.nl; FAX 31-10-4089468.
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Supplemental material is available at http://www.genesdev.org.
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Article is online at http://www.genesdev.org/cgi/doi/10.1101/gad.399506.
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- Received March 14, 2006.
- Accepted June 12, 2006.
- Copyright © 2006, Cold Spring Harbor Laboratory Press