PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE REVERSES THE INHIBITION OF RNA-TRANSCRIPTION CAUSED BY HISTONE H1

Phosphatidylinositol 4,5-bisphosphate [PtdIns(4, 5)P-2] has been known to bind to the pleckstrin homology domain and the phosphotyrosine-bin ding domain as well as actin-binding proteins, and to regulate their f unctions. We have tried to find new PtdIns(4,5)P-2-binding proteins an d to clarify the physiological effects of PtdIns(4,5)P-2 on their func tion. We report here that histones H1 and H3 are PtdIns(4,5)P-2-bindin g proteins which were identified using antibodies specific to PtdIns(4 ,5)P-2, H1, and H3. This binding was further confirmed by extracting P tdIns(4,5)P-2 from purified histone H1 and H3. Furthermore, the bindin g site of PtdIns(4,5)P-2 in histone H1 was found in the carboxyl-termi nal 103 amino acids. It was also shown that the amounts of PtdIns(4,5) P-2 bound to H1 decrease when histone H1 is phosphorylated by protein kinase C but not by protein kinase A or cdc2 kinase, in vitro. The pro tein kinase C phosphorylation site is localized close to the PtdIns(4, 5)P-2-binding site, suggesting that phosphorylation of histone H1 by p rotein kinase C interferes stereostructually with PtdIns(4,5)P-2 bindi ng. We further noticed that PtdIns(4,5)P-2 binding to H1 counteracts t he histone H1-mediated repression of basal transcription by RNA polyme rase II in a Drosophila transcription system in vitro. Phosphatidylino sitol 4-phosphate and phosphatidylinositol 3,4,5 trisphosphate affect this transcription activity more weakly than PtdIns(4,5)P-2 but PtdIns and other acidic lipids have no effect on this activity. These data i ndicate that PtdIns(4,5)P-2 bound to nuclear protein histone H1 may co ntribute to the regulation of transcription in eukaryotic cells.