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Key mediators of the enhancer blocker function of Drosophila CTCF

Functional eukaryotic gene units including all of their regulatory elements are insulated from each other to allow the action of regulatory elements on the appropriate gene. We and others have analyzed the DNA binding factor CTCF, which is the only protein known to mediate a directional blocking activity of enhancer elements in vertebrates. In focusing on Drosophila CTCF, we found out that dCTCF mediates enhancer blocking on the Fab-8insulator and binds to several other known insulator sequences. One set of dCTCF binding sites separates the homeotic genes responsible for the segmental identity in flies. Chromosomal binding sites are non-redundant with other insulator proteins BEAF-32 and Su(Hw). Overexpression or deletion of dCTCF are deleterious in flies, but not in cell culture, indicating an important developmental role. Current analyses is addressing the biological function in early embryogenesis and somatic tissues, and the characterization of different chromatin domains, of interaction partners and of genome-wide binding sites.

 

Funding:

SFB: TRR81 Giessen / Bad Nauheim, Marburg, Rotterdam