Publication Date:
2014-08-01
Description:
Protein arginine methyltransferase 6 (PRMT6) is a nuclear enzyme that modifies histone tails. To help elucidate the biological function of PRMT6 in vivo , we generated transgenic mice that ubiquitously express PRMT6 fused to the hormone-binding portion of the estrogen receptor (ER*). The ER*-PRMT6 fusion is unstable and cytoplasmic, but upon systemic treatment with tamoxifen, it becomes stabilized and translocates into the nucleus. As a result, a dramatic increase in the H3R2me2a histone mark is observed. We found that one consequence of induced ER*-PRMT6 activation is increased IL-6 levels. IL-6 expression is regulated by the nuclear factor-kappa B (NF-B) transcription factor, and PRMT6 functions as a coactivator of this pathway. We show that PRMT6 directly interacts with RelA, and that its overexpression enhances the transcriptional activity of an ectopic NF-B reporter and endogenously regulates NF-B target genes. PRMT6 is recruited, by RelA, to selective NF-B target promoters upon TNF-α stimulation. Moreover, ER*-PRMT6 activation causes RelA accumulation in the nucleus. In summary, we observe that PRMT6 is recruited to chromatin at selective NF-B target promoters, where it likely impacts the histone code and/or methylates other chromatin-associated proteins to facilitate transcription.
Print ISSN:
0305-1048
Electronic ISSN:
1362-4962
Topics:
Biology
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