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http://hdl.handle.net/2440/52530
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Type: | Journal article |
Title: | dLKR/SDH regulates hormone-mediated histone arginine methylation and transcription of cell death genes |
Author: | Cakouros, D. Mills, K. Denton, D. Paterson, A. Daish, T. Kumar, S. |
Citation: | Journal of Cell Biology, 2008; 182(3):481-495 |
Publisher: | Rockefeller Univ Press |
Issue Date: | 2008 |
ISSN: | 0021-9525 0021-9525 |
Statement of Responsibility: | 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 |
RMID: | 0020082326 |
DOI: | 10.1083/jcb.200712169 |
Appears in Collections: | Medicine publications |
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