The direct interaction between ASH2, a Drosophila trithorax group protein, and SKTL, a nuclear phosphatidylinositol 4-phosphate 5-kinase, implies a role for phosphatidylinositol 4,5-bisphosphate in maintaining transcriptionally active chromatin.
The products of trithorax group (trxG) genes maintain active transcription of many important developmental regulatory genes, including homeotic genes. Several trxG proteins have been shown to act in multimeric protein complexes that modify chromatin structure. ASH2, the product of the Drosophila trxG gene absent, small, or homeotic discs 2 (ash2) is a component of a 500-kD complex. In this article, we provide biochemical evidence that ASH2 binds directly to Skittles (SKTL), a predicted phosphatidylinositol 4-phosphate 5-kinase, and genetic evidence that the association of these proteins is functionally significant. We also show that histone H1 hyperphosphorylation is dramatically increased in both ash2 and sktl mutant polytene chromosomes. These results suggest that ASH2 maintains active transcription by binding a producer of nuclear phosphoinositides and downregulating histone H1 hyperphosphorylation.
Department of Biology, Johns Hopkins University, Baltimore, Maryland 21218, USA.
Mimi K
MK
Cheng
Allen
A
Shearn
D000595:Amino Acid Sequence; D000818:Animals; D002843:Chromatin / Q000235:genetics / Q000378:metabolism*; D029721:Drosophila Proteins / Q000235:genetics / Q000378:metabolism*; D004331:Drosophila melanogaster / Q000235:genetics*; D005455:Fluorescent Antibody Technique; D005982:Glutathione Transferase; D006657:Histones / Q000378:metabolism; D015151:Immunoblotting; D007150:Immunohistochemistry; D047468:Immunoprecipitation; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics / Q000378:metabolism*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics*; D020798:Two-Hybrid System Techniques
D002843:Chromatin; D029721:Drosophila Proteins; D006657:Histones; D009687:Nuclear Proteins; D019269:Phosphatidylinositol 4,5-Diphosphate; D014157:Transcription Factors; C103604:ash2 protein, Drosophila; D005982:Glutathione Transferase; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase