TranscriptionRegulationbyMethyltransferaseofCARM1

Several forms of post-translational modification regulate protein activities. Recently, protein methylation by CARM1 (coactivator-associated arginine methyltransferase 1) has been observed to play a key role in transcriptional regulation. CARM1 associates with the p160 class of transcriptional coactivators involved in gene activation by steroid hormone family receptors. CARM1 also interacts with CBP/p300 transcriptional coactivators involved in gene activation by a large variety of transcription factors, including steroid hormone receptors and CEBP. One target of CARM1 is the core histones H3 and H4, which are also targets of the histone acetylase activity of CBP/p300 coactivators. Recruitment of CARM1 to the promoter region by binding to coactivators increases histone methylation and makes promoter regions more accessible for transcription. Another target of CARM1 methylation is a coactivator it interacts with, CBP. Methylation of CBP by CARM1 blocks CBP from acting as a coactivator for CREB and redirects the limited CBP pool in the cell to be available for steroid hormone receptors. Other forms of post-translational protein modification such as phosphorylation are reversible in nature, but as of yet a protein demethylase is not known.

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REFERENCES: Dagang Chen, et al. Regulation of Transcription by a Protein Methyltransferase. Science, June 1999, Vol 284, 2174-2177. Dagang Chen, Shih-Ming Huang, and Michael R. Stallup. Synergistic, p160 Coactivator-dependent Enhancement of Estrogen Receptor Function by CARM1 and p300. The Journal of Biological Chemistry, December 2000, Vol 275, 40810-40816. Ma, H. et al. (2001) Hormone-dependent, CARM1-directed, arginine-specific methylation of histone H3 on a steroid-regulated promoter. Curr. Biol. 11(24), 1981-5 Wei Xu, et al. A Transcriptional Switch Mediated by Cofactor Methylation. Science, Vol 294, December 2001, 2507-2511.