Thyroid hormone receptor recruits histone methyltransferase PRMT1 to regulate transcription and developmental rate

Abstract

Protein arginine methyltransferase 1 (PRMT1) acts as a coactivator for nuclear receptors through histone H4 R3 methylation. Here we investigated the role of PRMT1 in thyroid hormone (T3) receptor (TR)‐mediated transcription in vivo during vertebrate development by using T3‐dependent Xenopus laevis metamorphosis as a model. We first showed that PRMT1 expression was upregulated during metamorphosis when both TR and T3 were present. We then demonstrated a role of 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 chromatin 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. Mechanistically, we showed that overexpression of PRMT1 enhanced TR binding to TREs in vivo, leading to increased histone modifications and recruitment of other coactivators. Importantly, transgenic overexpression of PRMT1 enhanced gene activation in vivo and accelerated both natural and T3‐induced metamorphosis. These results indicate that PRMT1 functions transiently as a coactivator in TR‐mediated transcription by enhancing TR‐TRE binding to regulate the rate of metamorphosis.