Interaction between the two ubiquitously expressed transcription factors NF-Y and Sp1

Roder, Karim; Wolf, Siegmund S.; Larkin, Kimberly; Schweizer, Michael

doi:10.1016/s0378-1119(99)00180-8

Cited by 104 publications

(81 citation statements)

References 35 publications

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“…We also demonstrated that this specific interaction occurred in vitro using GST pull-down assays. Very recently, a physical interaction between NF-YA and Sp1 has been demonstrated (46). The results of this study showed that the amino acid sequence between 55 and 134 of NF-YA interacts with the amino acid sequence between 139 and 344 of Sp1.…”

Section: Discussionmentioning

confidence: 52%

Sp Family Members and Nuclear Factor-Y Cooperatively Stimulate Transcription from the Rat Pyruvate Kinase M Gene Distal Promoter Region via Their Direct Interactions

Yamada¹,

Tanaka²,

Miyamoto³

et al. 2000

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 52%

Sp Family Members and Nuclear Factor-Y Cooperatively Stimulate Transcription from the Rat Pyruvate Kinase M Gene Distal Promoter Region via Their Direct Interactions

Yamada¹,

Tanaka²,

Miyamoto³

et al. 2000

Journal of Biological Chemistry

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“…A similar case may be the promoters of fatty acid synthase and the LDL receptor gene which require the SREBP-1 and generic co-regulator Sp1 for synergistic activation (34,40). Recently, the synergistic activation by SREBP-1 and Sp1 has also been reviewed on an artificially assembled chromatin template in vitro and Sp1 has been shown to interact with NF-Ya in vitro in the absence of DNA (41,42). Hence, it is believed that an interaction between NF-Y and Sp1 plays a crucial role in the sterol regulation of rat Dhcr7 promoter.…”

Section: Discussionmentioning

confidence: 99%

Cholesterol Biosynthesis from Lanosterol

Kim

Lee

Paik

2001

Journal of Biological Chemistry

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The 7-dehydrocholesterol reductase (Dhcr7) is the terminal enzyme in the pathway of cholesterol biosynthesis. We have previously reported that sterol depletion in vivo caused a significant induction of both liver mRNA and enzyme activity of Dhcr7 (Bae, S.-H., Lee, J. N., Fitzky, B. U., Seong, J., and Paik, Y.-K. (1999) J. Biol. Chem. 274, 14624 -14631). In this paper, we also observed liver cell-specific sterol-mediated Dhcr7 gene induction in vitro by sterol depletion in rat hepatoma cells, suggesting the presence of sterol-mediated regulatory elements in the Dhcr7 gene. To understand the mechanisms responsible for regulating Dhcr7 expression, we have isolated the 5-flanking region of the gene encoding rat Dhcr7 and have characterized the potential regulatory elements of the gene that are responsible for sterolmediated regulation. The Dhcr7 promoter contains binding sites for Sp1 (at ؊177, ؊172, ؊125, and ؊20), NF-Y (at ؊88 and ؊51), and SREBP-1 or ADD1 (at ؊33). Deletion analysis of the Dhcr7 gene promoter (؊1053/ ؉31), employing a nested series of Dhcr7-luciferase constructs, demonstrated that the ؊179 upstream region of the gene is necessary and sufficient for optimal efficient sterol-regulated transcription. DNase I footprinting and electrophoretic mobility shift assay showed that the SRE1/E box (؊33/؊22) involved in sterol response of many sterol-related enzyme genes was protected specifically by the overexpressed recombinant ADD1. Mutational analysis for the functional relationship between the identified cis-elements in this region indicate that one of the binding sites for Sp1 (GC box at ؊125) and NF-Y (CCAAT box at ؊88) plays a cooperative role in the sterol-mediated activation, in which the latter site also acts as a co-regulator for SREBP-activated Dhcr7 promoter activity. We believe that Dhcr7 is the first enzyme characterized with a sterol-regulatory function in the post-lanosterol pathway. This may be important for understanding the coordinated control of cholesterol biosynthesis as well as the molecular mechanism of SmithLemli-Opitz syndrome-related protein in mammals.

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“…By using the yeast two-hybrid system, the interaction of NF-Ya with Sp-1 has also been demonstrated (45). In addition, NF-Ya has been shown to interact with Sp-1 in vitro in the absence of DNA (45).…”

Section: Discussionmentioning

confidence: 99%

“…In addition, NF-Ya has been shown to interact with Sp-1 in vitro in the absence of DNA (45). Hence, it is possible that an interaction between NF-Y and Sp-1 might also play a role in the sterol response of human FAS promoter I.…”

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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Interaction between the two ubiquitously expressed transcription factors NF-Y and Sp1

Cited by 104 publications

References 35 publications

Sp Family Members and Nuclear Factor-Y Cooperatively Stimulate Transcription from the Rat Pyruvate Kinase M Gene Distal Promoter Region via Their Direct Interactions

Sp Family Members and Nuclear Factor-Y Cooperatively Stimulate Transcription from the Rat Pyruvate Kinase M Gene Distal Promoter Region via Their Direct Interactions

Cholesterol Biosynthesis from Lanosterol

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

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