MYOD and HAND transcription factors have conserved recognition sites in mTOR promoter: insights from in silico analysis.

Abstract

mTOR regulates multiple cellular processes that are critical for proper maintenance of cell growth and development. However, mechanisms and factors responsible for transcriptional regulation of mTOR are partially known. To identify different transcription factor binding sites in promoter region of mTOR, we performed in silico phylogenetic foot printing analysis of diverse set of human orthologs. Phylogenetic tree for the orthologs was generated to establish the evolutionary relationships among them. Conserved binding sites among the species were predicted by tool MEME. The predicted conserved sites were further analyzed for binding of transcription factors by MatInspector program. Predicted TFs were then integrated with known physical interactions and coexpression data to decipher the important transcriptional regulators of mTOR signaling. Our study suggests that motifs AGGCGGG (+ 15 to + 21) and GGCGGC (+ 60 to + 65) are highly conserved across the species and are recognition sequence for HAND and MYOD transcription factors, respectively. Also these two transcription factors show direct physical interaction in protein-protein interaction map, indicating their regulatory role on expression of mTOR for control of myogenesis. Our study provides novel clues on differential regulation of mTOR under diverse environmental conditions.