SAP18 promotes Krüppel-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 Krüppel 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. Krüppel mediates their transcriptional repression by direct association with the corepressor Drosophila C terminus-binding protein (dCtBP). However, for some Krüppel target genes, deletion of the dCtBP-binding sites does not abolish repression, implying a dCtBP-independent mode of repression. We identified Krüppel-binding proteins by mass spectrometry and found that SAP18 can both associate with Krüppel and support Krüppel-dependent repression. Genetic interaction studies combined with pharmacological and biochemical approaches suggest a site-specific mechanism of Krüppel-dependent gene silencing. The results suggest that Krüppel tethers the SAP18 bound histone deacetylase complex 1 at distinct enhancer elements, which causes repression via histone H3 deacetylation.
Matyash
Alexey
A
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany.
Singh
Navjot
N
Wadsworth Center, New York State Department of Health and Department of Biomedical Sciences, State University of New York, Albany, New York 12208.
Hanes
Steven D
SD
Wadsworth Center, New York State Department of Health and Department of Biomedical Sciences, State University of New York, Albany, New York 12208.
Urlaub
Henning
H
Bioanalytical Mass Spectrometry Group, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany.
Jäckle
Herbert
H
Abteilung Molekulare Entwicklungsbiologie, Max-Planck-Institut für biophysikalische Chemie, Am Fassberg 11, 37077 Göttingen, Germany. Electronic address: hjaeckl@gwdg.de.
D000107:Acetylation; D000595:Amino Acid Sequence; D000818:Animals; D002352:Carrier Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D029721:Drosophila Proteins / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D004331:Drosophila melanogaster; D004742:Enhancer Elements, Genetic; D006657:Histones / Q000378:metabolism*; D017403:In Situ Hybridization; D051741:Kruppel-Like Transcription Factors / Q000378:metabolism / Q000502:physiology*; D008969:Molecular Sequence Data; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction; D011485:Protein Binding; D019032:Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization; D014157:Transcription Factors / Q000737:chemistry / Q000378:metabolism / Q000502:physiology*; D014158:Transcription, Genetic / Q000502:physiology*
D002352:Carrier Proteins; D029721:Drosophila Proteins; D006657:Histones; C497244:Kr protein, Drosophila; D051741:Kruppel-Like Transcription Factors; D014157:Transcription Factors; C407043:bicoid interacting protein 1, Drosophila