Please use this identifier to cite or link to this item: 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
Appears in Collections:Aurora harvest 5
Medicine publications

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