Key result
PDX-1 and HNF-4 overexpression stimulates SREBP-1c gene expression, identifying them as novel regulators.
Why the study?
The transcriptional regulation of human SREBP-1c, a key regulator of lipogenesis, and its promoter characteristics were not fully understood.
Identification of PDX-1 and HNF-4 as transcription factors that stimulate human SREBP-1c gene expression provides new insights into the regulation of lipogenesis.
May guide lipogenesis research; leaves open translation to human cardiometabolic disease.
Sterol-regulatory-element-binding protein 1c (SREBP-1c) is one member of the family of transcription factors that stimulate sterol and fatty-acid biosynthesis in animal cells. Human SREBP-1c, mapped to chromosome 17p11.2, is expressed in liver, intestine, skeletal muscle and adipocytes. A section of genomic sequence from a chromosome 17 library, thought to contain the SREBP-1c promoter, was cloned. Putative transcription-factor-binding sites and a potential transcriptional start site were identified using the Genomatix Suite of sequence analysis tools (MatInspector). Sequence analysis showed the human promoter to be 42% identical with the previously published mouse sequence. Two novel transcription-factor-binding sites were identified: those for PDX-1 (pancreatic-duodenal homoeobox-1) and HNF-4 (hepatic nuclear factor-4). Co-transfection experiments with overexpression plasmids for PDX-1 and HNF-4 suggested that both factors stimulate SREBP-1c gene expression, although further work is required to ascertain their mechanisms of action.
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Tarling et al. (2004) studied this question. Co-transfection with overexpression plasmids for PDX-1 and HNF-4 was evaluated on SREBP-1c gene expression. Co-transfection with overexpression plasmids for PDX-1 and HNF-4 stimulated SREBP-1c gene expression, identifying them as novel regulators of this transcription factor.
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