Deciphering the Conserved Cis-Regulatory Elements of Major Milk Protein Genes by Computational Analysis
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Date
2024-04
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Addis Ababa University
Abstract
Milk genes are exclusively expressed in MECs during lactation, regulated by lactogenic hormones like prolactin that act through specific TFs. The recruitment of TF is determined by cis-regulatory motifs in their gene promoters; but there is limited evidence of shared motifs among the major milk gene across species. In this study, Jalview, Meme-Suite, TomTom, and GOMo software were utilized to construct phylogenetic trees, discover motifs, identify TFs, and determine GO terms, respectively, in the 2kb upstream putative promoter region of CSN1S1, CSN1S2, CSN2, CSN3, LALBA and BLG milk genes among twenty-three mammalian species. The analysis revealed three common TFBSs for STAT1, STAT5a, and STAT5b TFs in all milk genes across the species studied, except for BLG, within the region -390 to -80bp from the canonical TSS, with a few shared TFBSs located in the distal promoter region upstream of -600bp. STAT3 was also detected in CSN1S1, CSN2, CSN3, and LALBA genes, sharing binding sites with STAT1, STAT5a, and STAT5b. Furthermore, TFBSs for Sox9 and Sox6 TFs were found to be shared between the LALBA and BLG putative promoters within -400 to -100bp. Moreover, GO analysis linked GPCR with regulatory motifs in all six milk genes across 23 species, essential for enhancing STAT5 phosphorylation through Gαq activation in the JAK-STAT pathway. The totality of the result suggests that the relative abundance of STAT5 and STAT3 proteins may play a role in regulating the expression level of caseins and LALBA commensurate with the stage of lactation. Together, these results offer valuable insights into the potential of the milk genes’ promoter for constructing eukaryotic expression vectors and provide essential information for transgenic studies.
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Meme-Suite, Promoter, Cis-Regulatory Element, Motifs, Mammals, Mammary Gland, Milk Genes