Cooperative Binding of NF-Y and Sp1 at the DNase I-hypersensitive Site, Fatty Acid Synthase Insulin-responsive Element 1, Located at −500 in the Rat Fatty Acid Synthase Promoter

Roder, Karim; Wolf, Siegmund S.; Beck, Karl‐Friedrich; Schweizer, Michael

doi:10.1074/jbc.272.34.21616

Cited by 67 publications

(62 citation statements)

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“…The NF-Y-binding site in the rat FAS promoter is also involved in the cAMP-mediated response of the rat FAS promoter (35,36). The cooperative binding of NF-Y and Sp-1 in rat FAS insulin response has been shown (44).…”

Section: Discussionmentioning

confidence: 99%

Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites

Xiong

Chirala

Wakil

2000

Proc. Natl. Acad. Sci. U.S.A.

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To understand cholesterol-mediated regulation of human fatty acid synthase promoter I, we tested various 5 -deletion constructs of promoter I-luciferase reporter gene constructs in HepG2 cells. The reporter gene constructs that contained only the Sp-1-binding site (nucleotides ؊82 to ؊74) and the two tandem sterol regulatory elements (SREs; nucleotides ؊63 to ؊46) did not respond to cholesterol. Only the reporter gene constructs containing a nuclear factor-Y (NF-Y) sequence, the CCAAT sequence (nucleotides ؊90 to ؊86), an Sp-1 sequence, and the two tandem SREs responded to cholesterol. The NF-Y-binding site, therefore, is essential for cholesterol response. Mutating the SREs or the NF-Y site and inserting 4 bp between the Sp-1-and NF-Y-binding sites both resulted in a minimal cholesterol response of the reporter genes. Electrophoretic mobility-shift assays using anti-SRE-binding protein (SREBP) and anti-NF-Ya antibodies confirmed that these SREs and the NF-Y site bind the respective factors. We also identified a second Sp-1 site located between nucleotides ؊40 and ؊30 that can substitute for the mutated Sp-1 site located between nucleotides ؊82 and ؊74. H umans, like other animals, derive long-chain fatty acids either from food or by de novo synthesis from acetyl-CoA. De novo synthesis requires the participation of two multifunctional enzymes, fatty acid synthase (FAS; EC 2.3.1.85) and acetyl-CoA carboxylase (EC 6.4.1.2) (1). The regulation of animal FAS by diet and hormones is well documented (2). A fat-free carbohydrate-rich diet induces the synthesis of FAS and, consequently, an increase in the metabolic levels of long-chain fatty acids (1, 2). The levels of FAS are controlled by the rate of transcription and by the stability of its mRNA (2, 3). The regulation of animal FAS mRNA levels by the thyroid hormone and by insulin has been demonstrated (2, 3).Recent studies on cholesterol-mediated regulation of rat acetyl-CoA carboxylase (4, 5), rat FAS promoter I (6, 7), and stearoyl-CoA desaturase 1 (8, 9) suggest that lipogenesis and sterol synthesis and uptake are all coordinately regulated by cholesterol. Sterol-mediated regulation is facilitated by sterol regulatory element (SRE)-binding proteins (SREBPs) (10-14). SREBPs were originally characterized as transcription factors that regulate the genes involved in cholesterol uptake from plasma, such as the low-density lipoprotein receptor (15,16), and the genes involved in the biosynthetic pathway of cholesterol and lipids, such as 3-hydroxy-3-methylglutaryl-CoA (HMG-CoA) synthase, HMG-CoA reductase (17, 18), farnesyl diphosphate (FPP) synthase (19,20), squalene synthase (21, 22), and glycerol-3-phosphate acyltransferase (23).SREBPs are a novel family of membrane-bound transcription factors that contain the basic helix-loop-helix leucine zipper (24). When sterol levels are low, the membrane-bound precursor form of SREBP undergoes proteolytic cleavage in a two-step process that releases the N-terminal SREBP domain, which then enters the nucleus and binds to the SRE...

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Section: Discussionmentioning

confidence: 99%

Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites

Xiong

Chirala

Wakil

2000

Proc. Natl. Acad. Sci. U.S.A.

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“…Using IRE as the probe, three kinds of DNA-protein complex were formed: IRE:Sp1, IRE:CBF, and IRE:Sp1:CBF. The cooperation of Sp1 and CBF increased the stability of DNA-protein complex (Roder et al 1997). Because the distance between CBF and Sp1 seems to be critical for the synergism of CBF and Sp1 (Alimov et al 2005), their relationship in the control of a1-sGC subunit gene expression remains to be proven.…”

Section: Discussionmentioning

confidence: 99%

Molecular cloning and characterization of α1-soluble guanylyl cyclase gene promoter in rat pituitary cells

Jiang

Stojilković

2006

Journal of Molecular Endocrinology

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Soluble guanylyl cyclase is a cytosolic enzyme which catalyzes conversion of GTP to the second messenger cyclic GMP. The transcriptional regulation at the promoter levels of four soluble guanylyl cyclase subunits, termed a1, a2, b1, and b2, is largely unknown. In this study, we identified the transcription start site of a1-soluble guanylyl cyclase gene in rat pituitary cells and cloned the 3 . 5 kb 5 0 -promoter. Sequence analysis of this TATA-less promoter revealed the presence of several putative-binding sites for transcriptional factors, including CCAAT site at K41 to K32 and Sp1 site at K34 to K24. Transfection of pituitary cells with constructs of variable lengths confirmed the relevance of different promoter regions in the control of transcriptional activity. Among them, the K49 to C156 region was critical for basal transcriptional activity. Electrophoretic mobility shift assay using nuclear proteins extracted from normal and immortalized pituitary cells indicated that the CCAAT/Sp1 site within the K49 to C156 region was able to specifically interact with CCAAT-binding factor and Sp1. These two sites were partly overlapped and both of them conferred stimulatory effects. The in vivo recruitment of CCAAT-binding factor and Sp1 was confirmed by chromatin immunoprecipitation. These results indicate that the composite CCAAT/Sp1 cis-element contributes to the expression of a1-sGC subunit in resting pituitary cells.

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“…Our preliminary studies suggest that whereas overexpression of the AtLEC1 and AtL1L genes in other plant species, including rapeseed, is capable of stimulating the accumulation of lipids, overexpression of LEC1-like genes from other plant species can also significantly enhance FA biosynthesis in the transgenic Arabidopsis plants. In a more extended view, in mammalian cells, the CCAAT-binding factors directly bind to the FAS promoter and play an important role in the regulation of FAS gene expression (Rangan et al, 1996;Roder et al, 1997;Schweizer et al, 2002). Thus, this class of transcription factors is evolutionarily and functionally conserved in the regulation of FA biosynthesis.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Seed Oil Production in Canola by Conditional Expression of Brassica napus LEAFY COTYLEDON1 and LEC1-LIKE in Developing Seeds

et al. 2011

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The seed oil content in oilseed crops is a major selection trait to breeders. In Arabidopsis (Arabidopsis thaliana), LEAFY COTYLEDON1 (LEC1) and LEC1-LIKE (L1L) are key regulators of fatty acid biosynthesis. Overexpression of AtLEC1 and its orthologs in canola (Brassica napus), BnLEC1 and BnL1L, causes an increased fatty acid level in transgenic Arabidopsis plants, which, however, also show severe developmental abnormalities. Here, we use truncated napin A promoters, which retain the seed-specific expression pattern but with a reduced expression level, to drive the expression of BnLEC1 and BnL1L in transgenic canola. Conditional expression of BnLEC1 and BnL1L increases the seed oil content by 2% to 20% and has no detrimental effects on major agronomic traits. In the transgenic canola, expression of a subset of genes involved in fatty acid biosynthesis and glycolysis is up-regulated in developing seeds. Moreover, the BnLEC1 transgene enhances the expression of several genes involved in Suc synthesis and transport in developing seeds and the silique wall. Consistently, the accumulation of Suc and Fru is increased in developing seeds of the transgenic rapeseed, suggesting the increased carbon flux to fatty acid biosynthesis. These results demonstrate that BnLEC1 and BnL1L are reliable targets for genetic improvement of rapeseed in seed oil production.

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Cooperative Binding of NF-Y and Sp1 at the DNase I-hypersensitive Site, Fatty Acid Synthase Insulin-responsive Element 1, Located at −500 in the Rat Fatty Acid Synthase Promoter

Abstract: In vitro

Cited by 67 publications

References 50 publications

Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites

Sterol regulation of human fatty acid synthase promoter I requires nuclear factor-Y- and Sp-1-binding sites

Molecular cloning and characterization of α1-soluble guanylyl cyclase gene promoter in rat pituitary cells

Enhanced Seed Oil Production in Canola by Conditional Expression of Brassica napus LEAFY COTYLEDON1 and LEC1-LIKE in Developing Seeds

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