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https://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: | The 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 |
DOI: | 10.1083/jcb.200712169 |
Published version: | http://dx.doi.org/10.1083/jcb.200712169 |
Appears in Collections: | Aurora harvest 5 Medicine publications |
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