| First Author | Di Lorenzo A | Year | 2014 |
| Journal | Nucleic Acids Res | Volume | 42 |
| Issue | 13 | Pages | 8297-309 |
| PubMed ID | 24939901 | Mgi Jnum | J:218132 |
| Mgi Id | MGI:5616704 | Doi | 10.1093/nar/gku530 |
| Citation | Di Lorenzo A, et al. (2014) A gain-of-function mouse model identifies PRMT6 as a NF-kappaB coactivator. Nucleic Acids Res 42(13):8297-309 |
| abstractText | 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-kappaB) 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-kappaB reporter and endogenously regulates NF-kappaB target genes. PRMT6 is recruited, by RelA, to selective NF-kappaB target promoters upon TNF-alpha stimulation. Moreover, ER*-PRMT6 activation causes RelA accumulation in the nucleus. In summary, we observe that PRMT6 is recruited to chromatin at selective NF-kappaB target promoters, where it likely impacts the histone code and/or methylates other chromatin-associated proteins to facilitate transcription. |
