title: CTCF is conserved from Drosophila to humans and confers enhancer blocking of the Fab-8 insulator.
abstract: Eukaryotic transcriptional regulation often involves regulatory elements separated from the cognate genes by long distances, whereas appropriately positioned insulator or enhancer-blocking elements shield promoters from illegitimate enhancer action. Four proteins have been identified in Drosophila mediating enhancer blocking-Su(Hw), Zw5, BEAF32 and GAGA factor. In vertebrates, the single protein CTCF, with 11 highly conserved zinc fingers, confers enhancer blocking in all known chromatin insulators. Here, we characterize an orthologous CTCF factor in Drosophila with a similar domain structure, binding site specificity and transcriptional repression activity as in vertebrates. In addition, we demonstrate that one of the insulators (Fab-8) in the Drosophila Abdominal-B locus mediates enhancer blocking by dCTCF. Therefore, the enhancer-blocking protein CTCF and, most probably, the mechanism of enhancer blocking mediated by this remarkably versatile factor are conserved from Drosophila to humans.
authors.affiliation: Section of Molecular Pathology, Laboratory of Immunopathology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland 20852, USA.
authors.forename: Hanlim
authors.initials: H
authors.lastname: Moon
authors.forename: Galina
authors.initials: G
authors.lastname: Filippova
authors.forename: Dmitry
authors.initials: D
authors.lastname: Loukinov
authors.forename: Elena
authors.initials: E
authors.lastname: Pugacheva
authors.forename: Qi
authors.initials: Q
authors.lastname: Chen
authors.forename: Sheryl T
authors.initials: ST
authors.lastname: Smith
authors.forename: Adam
authors.initials: A
authors.lastname: Munhall
authors.forename: Britta
authors.initials: B
authors.lastname: Grewe
authors.forename: Marek
authors.initials: M
authors.lastname: Bartkuhn
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Arnold
authors.forename: Les J
authors.initials: LJ
authors.lastname: Burke
authors.forename: Renate
authors.initials: R
authors.lastname: Renkawitz-Pohl
authors.forename: Rolf
authors.initials: R
authors.lastname: Ohlsson
authors.forename: Jumin
authors.initials: J
authors.lastname: Zhou
authors.forename: Rainer
authors.initials: R
authors.lastname: Renkawitz
authors.forename: Victor
authors.initials: V
authors.lastname: Lobanenkov
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D000076246:CCCTC-Binding Factor; D004268:DNA-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D004330:Drosophila / Q000235:genetics* / Q000378:metabolism; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation / Q000502:physiology; D018398:Homeodomain Proteins / Q000235:genetics* / Q000378:metabolism; D006801:Humans; D038101:Insulator Elements; D008969:Molecular Sequence Data; D012097:Repressor Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: C062393:Abd-B proteins, Drosophila; D000076246:CCCTC-Binding Factor; C000619697:CTCF protein, human; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; D018398:Homeodomain Proteins; D012097:Repressor Proteins