Transcriptional regulation of MSX1 natural antisense transcript

Abstract

Msx homeogenes play an important role in the epithelial-mesenchymal interactions leading development. Msx1 is relevant for dental and craniofacial morphogenesis, as suggested by phenotypes of Msx1 mutations in human and Msx1 KO mice. Our group showed that Msx1 gene expression can be regulated by a bidirectional transcription generating long noncoding antisense (AS) RNA the expression which is linked to the Msx1 sense (S) RNA level. Thus, the aim of the present study was to analyze the synthesis of Msx1 (AS) RNA. In vivo Msx1 AS expression analysis showed that (i) the putative promoter sequence but not the transcribed sequence was important and necessary for its expression, (ii) 2 different areas of alveolar bone can be distinguished depending on Msx1 S and AS expression, and (iii) Msx1 presence was necessary for Msx1 AS RNA full expression. In silico analysis of the Msx1 AS putative promoter region showed the presence of 4 Msx response elements possibly involved in Msx1 regulation. Msx1 constitutes an example of a bidirectionally transcribed gene giving rise to an S/AS RNA pair included in the big and growing family of AS noncoding RNAs. Our results contribute to defining a link between Msx1 S and AS RNAs resulting in a fine-tuned regulatory loop of Msx1 expression. The significance of this finding is that disturbance of the balance between Msx1 S and AS RNA status may be associated with tooth agenesis and bone loss.