title: TDRD3 is an effector molecule for arginine-methylated histone marks.
abstract: Specific sites of histone tail methylation are associated with transcriptional activity at gene loci. These methyl marks are interpreted by effector molecules, which harbor protein domains that bind the methylated motifs and facilitate either active or inactive states of transcription. CARM1 and PRMT1 are transcriptional coactivators that deposit H3R17me2a and H4R3me2a marks, respectively. We used a protein domain microarray approach to identify the Tudor domain-containing protein TDRD3 as a "reader" of these marks. Importantly, TDRD3 itself is a transcriptional coactivator. This coactivator activity requires an intact Tudor domain. TDRD3 is recruited to an estrogen-responsive element in a CARM1-dependent manner. Furthermore, ChIP-seq analysis of TDRD3 reveals that it is predominantly localized to transcriptional start sites. Thus, TDRD3 is an effector molecule that promotes transcription by binding methylarginine marks on histone tails.
authors.affiliation: The University of Texas MD Anderson Cancer Center, Science Park-Research Division, P.O. Box 389, Smithville, TX 78957, USA.
authors.forename: Yanzhong
authors.initials: Y
authors.lastname: Yang
authors.forename: Yue
authors.initials: Y
authors.lastname: Lu
authors.forename: Alexsandra
authors.initials: A
authors.lastname: Espejo
authors.forename: Jiacai
authors.initials: J
authors.lastname: Wu
authors.forename: Wei
authors.initials: W
authors.lastname: Xu
authors.forename: Shoudan
authors.initials: S
authors.lastname: Liang
authors.forename: Mark T
authors.initials: MT
authors.lastname: Bedford
mesh_terms: D001120:Arginine / Q000378:metabolism*; D053468:CARD Signaling Adaptor Proteins / Q000235:genetics / Q000378:metabolism*; D006162:Guanylate Cyclase / Q000235:genetics / Q000378:metabolism*; D006657:Histones / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008745:Methylation; D040081:Protein Array Analysis; D011484:Protein-Arginine N-Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012097:Repressor Proteins / Q000235:genetics / Q000378:metabolism*; D014158:Transcription, Genetic / Q000235:genetics
chemical_list: D053468:CARD Signaling Adaptor Proteins; D006657:Histones; D011506:Proteins; D012097:Repressor Proteins; C532746:Tdrd3 protein, human; D001120:Arginine; C099988:PRMT1 protein, human; D011484:Protein-Arginine N-Methyltransferases; C426242:CARD11 protein, human; D006162:Guanylate Cyclase