In:
British Journal of Nutrition, Cambridge University Press (CUP), Vol. 122, No. 11 ( 2019-12-14), p. 1201-1211
Abstract:
Disturbances in lipid metabolism are at the core of several health issues facing modern society, including fatty liver and obesity. The sterol regulatory element-binding protein 1 (SREBP-1) is one important transcription factor regulating lipid metabolism, but the relevant mechanism still remains unknown. The present study determined the transcriptional regulation of SREBP-1 and its target genes (including acetyl-CoA carboxylase α ( accα ), fatty acid synthase ( fas ) and stearoyl-CoA desaturase 1 ( scd 1)) in a freshwater teleost, grass carp Ctenopharyngodon idella . We cloned and characterised the 1988 bp, 2043 bp, 1632 bp and 1889 bp sequences of srebp -1, accα , scd 1 and fas promoters, respectively. A cluster of putative binding sites of transcription factors, such as specific protein, yin yang 1, nuclear factor Y, sterol response elements (SRE) and enhancer box (E-box) element, were predicted on their promoter regions. Overexpression of nSREBP-1 reduced srebp -1 promoter activity, increased scd 1 and fas promoter activity but did not influence accα promoter activity. The site-mutation and electrophoretic mobility shift assay analysis indicated that srebp- 1 , fas and scd 1 promoters, but not accα promoter, possessed SRE. In Ctenopharyngodon idella kidney (CIK) cells of grass carp, nSREBP-1 overexpression significantly reduced srebp -1 mRNA expression and up-regulated miR-29 mRNA expression. The 3′UTR of srebp- 1 possessed the potential miR-29 binding site and miR-29 up-regulated the luciferase activity of srebp- 1 3′UTR and srebp -1 mRNA expression, implying a self-activating loop of SREBP-1 and miR-29 in grass carp. Based on the above-mentioned results, we found two novel transcriptional mechanisms for SREBP-1 in grass carp: (1) the auto-regulation sited on the SREBP-1 promoter regions was suppressive and (2) there was a self-activating loop of SREBP-1 and miR-29.
Type of Medium:
Online Resource
ISSN:
0007-1145
,
1475-2662
DOI:
10.1017/S0007114519001934
Language:
English
Publisher:
Cambridge University Press (CUP)
Publication Date:
2019
detail.hit.zdb_id:
2016047-1
SSG:
12
SSG:
21
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