Abstract
Fat-induced transcript 1 (FIT1/FITM1) gene is a member of the conserved gene family important for triglyceride-rich lipid droplet accumulation. FIT1 gene displays a similar muscle-specific expression across pigs, mice, and humans. Thus pigs can act as a useful model of many human diseases resulting from misexpression of FIT1 gene. Triglyceride content in skeletal muscle plays a key role in pork meat quality and flavors. An insertion/deletion mutation in porcine FIT1 coding region shows a high correlation with a series of fat traits. To gain better knowledge of the potential role of FIT1 gene in human diseases and the correlations with pork meat quality, our attention is given to the region upstream of the porcine FIT1 coding sequence. We cloned ~1 kb of the 5′-flanking region of porcine FIT1 gene to define the role of this sequence in modulating the myogenic expression. A canonical E-box element that activated porcine FIT1 promoter activity during myogenesis was identified. Further analysis demonstrated that promoter activity was induced by overexpression of MyoD1, which bound to this canonical E-box during C2C12 differentiation. This is the first evidence that FIT1 as the direct novel target of MyoD is involved in muscle development.
Highlights
Fat-induced transcript 1 (FIT1/FITM1), named fat-inducing transcript 1, is a member of the conserved gene family, important for triglyceride-rich lipid droplet (LD)accumulation [1]
To further investigate whether FIT1 gene expression was regulated in a temporal manner during skeletal muscle development of swine, the expression of FIT1 mRNA was examined at various developmental stages, including embryonic, 2, 4, 6-month of age respectively (Figure S1A)
The data above demonstrates that the expression of FIT1 in C2C12 cells is induced with differentiation
Summary
Fat-induced transcript 1 (FIT1/FITM1), named fat-inducing transcript 1, is a member of the conserved gene family (including FIT1 and FIT2), important for triglyceride-rich lipid droplet (LD). Human FIT1 mRNA and protein showed a similar expression pattern with mice and pigs [1,4], suggesting the conserved role of FIT1 in regulating myogenic expression among these mammals. Murine FIT protein were both localized in endoplasmic reticulum (ER) with six-transmembrane-domains each, and mediated triglyceride-rich LD accumulation by direct binding to each protein [1,6,7]. This difference in expression pattern may reflect their individual unique function [7]. We further demonstrated that the activity of FIT1 promoter could be induced by MyoD1 which bound to this conserved E-box site
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