期刊
NUCLEIC ACIDS RESEARCH
卷 42, 期 13, 页码 8297-8309出版社
OXFORD UNIV PRESS
DOI: 10.1093/nar/gku530
关键词
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资金
- National Institutes of Health [NIH] [DK062248]
- Cancer Prevention and Research Institute of Texas (CPRIT) [RP110471]
- Schissler Foundation Fellowship
- Julia Jones Matthews Cancer Research Scholar Foundation
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-kappa 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-kappa B reporter and endogenously regulates NF-kappa B target genes. PRMT6 is recruited, by RelA, to selective NF-kappa B 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-kappa B target promoters, where it likely impacts the histone code and/or methylates other chromatin-associated proteins to facilitate transcription.
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