Selvi, B.R., Swaminathan, A., Maheshwari, U., Nagabhushana, A., Mishra, R., Kundu, T.K. (2015) CARM1 regulates astroglial lineage through transcriptional regulation of Nanog and posttranscriptional regulation by miR92a. Molecular biology of the cell. 26(2):316-26.
Coactivator associated arginine methyltransferase (CARM1/PRMT4) mediated transcriptional coactivation and arginine methylation is known to regulate various tissue-specific differentiation events. Although CARM1 is expressed in the neural crest region in early development, coinciding with early neuronal progenitor specification, the role of CARM1 in any neuronal developmental pathways has been unexplored. Using a specific small molecule inhibitor of CARM1-mediated H3R17 methylation in human embryonic stem cell line, we have identified that H3R17 methylation contributes to the maintenance of the astroglial cell population. A network of regulation was observed on the miR92a promoter wherein H3R17 responsive Nanog bound to the miR92a promoter was decreased upon inhibition resulting in an abnormal gene expression program influencing the glial lineage. This was also true in zebrafish, wherein, with the help of the CARM1 inhibitor and CARM1 morpholinos, we show that inhibition of H3R17 methylation results in defective glial cell morphology and a sensory defect in a subpopulation. A gain of function strategy where mCARM1 was introduced in the morpholino treated embryos, exhibited a recovery of the sensory defect phenotype. This report, thus establishes the functional cooperation between arginine methylation and miRNA expression in the neuronal developmental process with potential implications in sensory development pathways.