Protein phosphatase 2A activity affects histone H3 phosphorylation and transcription in Drosophila melanogaster.
Transcriptional activation of the heat shock genes during the heat shock response in Drosophila has been intimately linked to phosphorylation of histone H3 at serine 10, whereas repression of non-heat-shock genes correlates with dephosphorylation of histone H3. It is then possible that specific kinase and/or phosphatase activities may regulate histone phosphorylation and therefore transcription activation and repression, respectively. We find that treatment of cells with strong phosphatase inhibitors interferes with the genome-wide dephosphorylation of histone H3 normally observed at non-heat-shock genes during heat shock. Mutants in protein phosphatase type 2A (PP2A) also display reduced genome-wide H3 dephosphorylation, and sites of H3 phosphorylation that do not contain heat shock genes remain transcriptionally active during heat shock in PP2A mutants. Finally, the SET protein, a potent and highly selective inhibitor of PP2A activity that inhibits PP2A-mediated dephosphorylation of Ser10-phosphorylated H3, is detected at transcriptionally active regions of polytene chromosomes. These results suggest that activation and repression of gene expression during heat shock might be regulated by changes in PP2A activity controlled by the SET protein.
Nowak
Scott J
SJ
Department of Biology, The Johns Hopkins University, Baltimore, Maryland 21218, USA.
Pai
Chi-Yun
CY
Corces
Victor G
VG
D000818:Animals; D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins / Q000235:genetics* / Q000378:metabolism*; D004331:Drosophila melanogaster; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005786:Gene Expression Regulation; D018869:Heat-Shock Response / Q000187:drug effects / Q000235:genetics; D006657:Histones / Q000235:genetics* / Q000378:metabolism*; D007814:Larva; D009154:Mutation; D019319:Okadaic Acid / Q000494:pharmacology; D010749:Phosphoprotein Phosphatases / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation; D054648:Protein Phosphatase 2; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D012319:RNA Polymerase II / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D012469:Salivary Glands / Q000187:drug effects / Q000502:physiology; D012694:Serine / Q000378:metabolism; D014157:Transcription Factors; D014158:Transcription, Genetic
D002868:Chromosomal Proteins, Non-Histone; D029721:Drosophila Proteins; D004791:Enzyme Inhibitors; D006657:Histones; D011506:Proteins; D014157:Transcription Factors; D019319:Okadaic Acid; D012694:Serine; D012319:RNA Polymerase II; D010749:Phosphoprotein Phosphatases; D054648:Protein Phosphatase 2