Requirement for multiple domains of the protein arginine methyltransferase CARM1 in its transcriptional coactivator function.
The p160 coactivator complex plays a critical role in transcriptional activation by nuclear receptors and possibly other classes of DNA-binding transcriptional activators. The complex contains at least one of three p160 coactivators (SRC-1, GRIP1/TIF2, or pCIP/RAC3/ACTR/AIB1/TRAM1), a histone acetyltransferase such as CBP or p300, and the histone methyltransferase CARM1 (coactivator-associated arginine methyltransferase 1). Methylation of histone H3 and possibly other proteins in the transcription initiation complex by CARM1 occurs along with acetylation of histones and other proteins by CBP and p300 to help remodel chromatin structure and recruit RNA polymerase II. Here we show that other domains of CARM1 are required for the coactivator function of CARM1 in addition to the methyltransferase activity. The methyltransferase GRIP1, binding, and homo-oligomerization activities all reside in the central region of CARM1, which is highly conserved among the entire protein arginine methyltransferase family. In addition to this conserved domain, the unique N- and C-terminal regions of CARM1 were also required for enhancement of transcriptional activation by nuclear receptors. While the N-terminal region has no known activity at present, the C-terminal part of CARM1 contains an autonomous activation domain, suggesting that it interacts with other proteins that help to mediate CARM1 coactivator function.
D000818:Animals; D002460:Cell Line; D051958:Nuclear Receptor Coactivator 2; D011485:Protein Binding; D011484:Protein-Arginine N-Methyltransferases / Q000737:chemistry / Q000378:metabolism*; D011960:Receptors, Estrogen / Q000378:metabolism; D015534:Trans-Activators / Q000737:chemistry / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism
D051958:Nuclear Receptor Coactivator 2; D011960:Receptors, Estrogen; D015534:Trans-Activators; D014157:Transcription Factors; D011484:Protein-Arginine N-Methyltransferases; C119966:coactivator-associated arginine methyltransferase 1