RT Journal Article
SR Electronic
T1 CARM1 methylates MED12 to regulate its RNA-binding ability
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800117
DO 10.26508/lsa.201800117
VO 1
IS 5
A1 Donghang Cheng
A1 Vidyasiri Vemulapalli
A1 Yue Lu
A1 Jianjun Shen
A1 Sayura Aoyagi
A1 Christopher J Fry
A1 Yanzhong Yang
A1 Charles E Foulds
A1 Fabio Stossi
A1 Lindsey S Treviño
A1 Michael A Mancini
A1 Bert W O'Malley
A1 Cheryl L Walker
A1 Thomas G Boyer
A1 Mark T Bedford
YR 2018
UL https://www.life-science-alliance.org/content/1/5/e201800117.abstract
AB The coactivator-associated arginine methyltransferase (CARM1) functions as a regulator of transcription by methylating a diverse array of substrates. To broaden our understanding of CARM1's mechanistic actions, we sought to identify additional substrates for this enzyme. To do this, we generated CARM1 substrate motif antibodies, and used immunoprecipitation coupled with mass spectrometry to identify cellular targets of CARM1, including mediator complex subunit 12 (MED12) and the lysine methyltransferase KMT2D. Both of these proteins are implicated in enhancer function. We identified the major CARM1-mediated MED12 methylation site as arginine 1899 (R1899), which interacts with the Tudor domain–containing effector molecule, TDRD3. Chromatin immunoprecipitation–seq studies revealed that CARM1 and the methyl mark it deposits are tightly associated with ERα-specific enhancers and positively modulate transcription of estrogen-regulated genes. In addition, we showed that the methylation of MED12, at the R1899 site, and the recruitment of TDRD3 by this methylated motif are critical for the ability of MED12 to interact with activating noncoding RNAs.