Novel functions of protein arginine methyltransferase 1 in thyroid hormone receptor-mediated transcription and in the regulation of metamorphic rate in Xenopus laevis.
Protein arginine methyltransferase 1 (PRMT1) acts as a transcription coactivator for nuclear receptors through histone H4 R3 methylation. The in vivo function of PRMT1 is largely unknown. Here we investigated the role of PRMT1 in thyroid hormone (T3) receptor (TR)-mediated transcription in vivo during vertebrate development. By using intestinal remodeling during T3-dependent Xenopus laevis metamorphosis for in vivo molecular analysis, we first showed that PRMT1 expression was upregulated during metamorphosis when both TR and T3 were present. We then demonstrated a role for PRMT1 in TR-mediated transcription by showing that PRMT1 enhanced transcriptional activation by liganded TR in the frog oocyte transcription system and was recruited to the T3 response element (TRE) of the target promoter in the oocyte, as well as to endogenous TREs during frog metamorphosis. Surprisingly, we found that PRMT1 was only transiently recruited to the TREs in the target during metamorphosis and observed no PRMT1 recruitment to TREs at the climax of intestinal remodeling when both PRMT1 and T3 were at peak levels. Mechanistically, we showed that overexpression of PRMT1 enhanced TR binding to TREs both in the frog oocyte model system and during metamorphosis. More importantly, transgenic overexpression of PRMT1 enhanced gene activation in vivo and accelerated both natural and T3-induced metamorphosis. These results thus indicate that PRMT1 functions transiently as a coactivator in TR-mediated transcription by enhancing TR-TRE binding and further suggest that PRMT1 has tissue-specific roles in regulating the rate of metamorphosis.
Matsuda
Hiroki
H
Section on Molecular Morphogenesis, PCRM, NICHD, NIH, Bethesda, Maryland 20892, USA.
Paul
Bindu D
BD
Choi
Cheol Young
CY
Hasebe
Takashi
T
Shi
Yun-Bo
YB
D000818:Animals; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006657:Histones / Q000378:metabolism; D007422:Intestines / Q000187:drug effects / Q000201:enzymology / Q000254:growth & development; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D008675:Metamorphosis, Biological / Q000187:drug effects / Q000235:genetics*; D008745:Methylation / Q000187:drug effects; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding / Q000187:drug effects; D011484:Protein-Arginine N-Methyltransferases; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011988:Receptors, Thyroid Hormone / Q000378:metabolism*; D020218:Response Elements; D014158:Transcription, Genetic / Q000187:drug effects; D019076:Transgenes; D014284:Triiodothyronine / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D014982:Xenopus laevis / Q000235:genetics* / Q000254:growth & development*
D006657:Histones; D047908:Intracellular Signaling Peptides and Proteins; D008024:Ligands; D012333:RNA, Messenger; D011988:Receptors, Thyroid Hormone; D014284:Triiodothyronine; D008780:Methyltransferases; C077013:PRMT2 protein, human; D011484:Protein-Arginine N-Methyltransferases