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Protein arginine methyltransferase 5 (PRMT5) contributes positively to the induction of the E‐selectin gene in endothelial cells (EC) by binding to HOXA9
Author(s) -
Bandyopadhyay Smarajit,
Harris Daniel P.,
Lause Gregory,
Money Angela,
DiCorleto Paul E.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.637.5
Subject(s) - protein arginine methyltransferase 5 , chromatin immunoprecipitation , microbiology and biotechnology , transcription factor , biology , promoter , chemistry , methyltransferase , gene expression , gene , biochemistry , methylation
Multiple transcription factors, including the homeobox protein HOXA9, participate in cytokine induction of the EC‐leukocyte adhesion molecule E‐selectin in EC. HOX proteins often require other activators/co‐activators to affect rates of transcription. We have recently reported that HOXA9 associates with the type II protein arginine methyltransferase PRMT5 in TNF‐a‐activated EC. Although the cellular distribution and the protein level of PRMT5 were unaltered in EC in response to TNF, nuclear PRMT5 transiently associated with HOXA9. The kinetics of this binding was consistent with the association of these proteins with the E‐selectin promoter, as shown by chromatin immunoprecipitation (ChIP) assays. Specific depletion of PRMT5 protein by siRNA led to a significant decrease in both E‐selectin promoter activity and E‐selectin gene induction by TNF. Binding of HOXA9 to its recognition sequence was required for PRMT5 recruitment to the promoter, but not vice‐versa. Moreover, TNF‐dependent transient simultaneous association of both PRMT5 and a symmetrically dimethylated arginine (SDMA)‐containing protein was readily detected by ChIP. This latter protein appears to be distinct from HOXA9. These results demonstrate that HOXA9 recruits PRMT5 to the E‐selectin promoter where it acts as a transcriptional co‐activator. (NIH HL29582)