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|Title:||dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes|
|Citation:||Journal of Cell Biology, 2008; 182(3):481-495|
|Publisher:||Rockefeller Univ Press|
|Dimitrios Cakouros, Kathryn Mills, Donna Denton, Alicia Paterson, Tasman Daish, and Sharad Kumar|
|Abstract:||The sequential modifications of histones form the basis of the histone code that translates into either gene activation or repression. Nuclear receptors recruit a cohort of histone-modifying enzymes in response to ligand binding and regulate proliferation, differentiation, and cell death. In Drosophila melanogaster, the steroid hormone ecdysone binds its heterodimeric receptor ecdysone receptor/ultraspiracle to spatiotemporally regulate the transcription of several genes. In this study, we identify a novel cofactor, Drosophila lysine ketoglutarate reductase (dLKR)/saccharopine dehydrogenase (SDH), that is involved in ecdysone-mediated transcription. dLKR/SDH binds histones H3 and H4 and suppresses ecdysone-mediated transcription of cell death genes by inhibiting histone H3R17me2 mediated by the Drosophila arginine methyl transferase CARMER. Our data suggest that the dynamic recruitment of dLKR/SDH to ecdysone-regulated gene promoters controls the timing of hormone-induced gene expression. In the absence of dLKR/SDH, histone methylation occurs prematurely, resulting in enhanced gene activation. Consistent with these observations, the loss of dLKR/SDH in Drosophila enhances hormone-regulated gene expression, affecting the developmental timing of gene activation.|
|Keywords:||Cell Nucleus; Animals; Drosophila melanogaster; Ecdysone; Caspases; Saccharopine Dehydrogenases; Arginine; Drosophila Proteins; Histones; Receptors, Steroid; Cell Death; Transcription, Genetic; Gene Expression Regulation, Developmental; RNA Interference; Binding Sites; Protein Binding; Methylation; Protein Transport; Kinetics; Genes, Insect; Models, Genetic; Promoter Regions, Genetic; Transcriptional Activation|
|Appears in Collections:||Medicine publications|
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