Evolutionary-driven C-MYC gene expression in mammalian fibroblasts.

Publisher: Nature Publishing Group Country of Publication: England NLM ID: 101563288 Publication Model: Electronic Cited Medium: Internet ISSN: 2045-2322 (Electronic) Linking ISSN: 20452322 NLM ISO Abbreviation: Sci Rep Subsets: MEDLINE

Original Publication: London : Nature Publishing Group, copyright 2011-

Evolution, Molecular* ; Genes, myc*; Cattle/*genetics ; Sheep, Domestic/*genetics; Amino Acid Sequence ; Animals ; Cattle/metabolism ; Cyclin-Dependent Kinase 9/genetics ; Fibroblasts/metabolism ; Gene Expression ; Protein Processing, Post-Translational ; Proto-Oncogene Proteins c-myc/genetics ; Proto-Oncogene Proteins c-myc/metabolism ; Regulatory Elements, Transcriptional ; Sequence Homology, Amino Acid ; Sheep, Domestic/metabolism ; Species Specificity ; T-Box Domain Proteins/genetics ; Transcriptome

The extent to which mammalian cells share similar transcriptomes remains unclear. Notwithstanding, such cross-species gene expression inquiries have been scarce for defined cell types and most lack the dissection of gene regulatory landscapes. Therefore, the work was aimed to determine C-MYC relative expression across mammalian fibroblasts (Ovis aries and Bos taurus) via cross-species RT-qPCR and comprehensively explore its regulatory landscape by in silico tools. The prediction of transcription factor binding sites in C-MYC and its 2.5 kb upstream sequence revealed substantial variation, thus indicating evolutionary-driven re-wiring of cis-regulatory elements. C-MYC and its downstream target TBX3 were up-regulated in Bos taurus fibroblasts. The relative expression of C-MYC regulators [RONIN (also known as THAP11), RXRβ, and TCF3] and the C-MYC-associated transcript elongation factor CDK9 did not differ between species. Additional in silico analyses suggested Bos taurus-specific C-MYC exonization, alternative splicing, and binding sites for non-coding RNAs. C-MYC protein orthologs were highly conserved, while variation was in the transactivation domain and the leucine zipper motif. Altogether, mammalian fibroblasts display evolutionary-driven C-MYC relative expression that should be instructive for understanding cellular physiology, cellular reprogramming, and C-MYC-related diseases.

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0 (Proto-Oncogene Proteins c-myc)
0 (T-Box Domain Proteins)
EC 2.7.11.22 (Cyclin-Dependent Kinase 9)

Date Created: 20200708 Date Completed: 20201221 Latest Revision: 20210706

20240829

PMC7338511

10.1038/s41598-020-67391-x

32632086