SAP18 promotes Krueppel-dependent transcriptional repression by enhancer-specific histone deacetylation.

Body pattern formation during early embryogenesis of Drosophila melanogaster relies on a zygotic cascade of spatially restricted transcription factor activities. The gap gene Krueppel ranks at the top level of this cascade. It encodes a C2H2 zinc finger protein that interacts directly with cis-acting stripe enhancer elements of pair rule ...
genes, such as even skipped and hairy, at the next level of the gene hierarchy. Krueppel mediates their transcriptional repression by direct association with the corepressor Drosophila C terminus-binding protein (dCtBP). However, for some Krueppel target genes, deletion of the dCtBP-binding sites does not abolish repression, implying a dCtBP-independent mode of repression. We identified Krueppel-binding proteins by mass spectrometry and found that SAP18 can both associate with Krueppel and support Krueppel-dependent repression. Genetic interaction studies combined with pharmacological and biochemical approaches suggest a site-specific mechanism of Krueppel-dependent gene silencing. The results suggest that Krueppel tethers the SAP18 bound histone deacetylase complex 1 at distinct enhancer elements, which causes repression via histone H3 deacetylation.
Mesh Terms:
Acetylation, Amino Acid Sequence, Animals, Carrier Proteins, Drosophila Proteins, Drosophila melanogaster, Enhancer Elements, Genetic, Histones, In Situ Hybridization, Kruppel-Like Transcription Factors, Molecular Sequence Data, Oligonucleotide Array Sequence Analysis, Polymerase Chain Reaction, Protein Binding, Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization, Transcription Factors, Transcription, Genetic
J. Biol. Chem.
Date: Jan. 30, 2009
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