Human Fatty-acid Synthase Gene

Hsu, Matthew; Chirala, Subrahmanyam S.; Wakil, Salih J.

doi:10.1074/jbc.271.23.13584

Cited by 46 publications

(29 citation statements)

References 45 publications

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“…This motif is found in the promoter of glyceraldehyde-3-phosphate dehydrogenase gene (39). At position Ϫ198, the sequence closely matched that of the fat-specific element 1 (FSE1) of the fatty acid synthase gene (TCAGGGCCCAGGAACTG) (40). The presence of the FSE1 in the proximal promoter suggested that this promoter may mediate the transcripts that are used under lipogenic conditions as we have previously shown that these transcripts were detected in both abdominal and epididymal fat tissues (17).…”

Section: Organization Of the Coding Exons-mentioning

confidence: 81%

“…FSE1 has been shown to be involved in the regulation of genes whose expression is closely linked to adipocyte differentiation. These include the putative fatty acid binding protein (ap2) (41), glyceraldehyde-3-phosphate dehydrogenase (42), adipsin, acyl-CoA synthetase, fatty acid synthase (40). There were also eleven copies of the unusual motif, TCCCC or TCCCCC arranged as direct or inverted repeats (boxed) (Fig.…”

Section: Organization Of the Coding Exons-mentioning

confidence: 99%

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The Rat Pyruvate Carboxylase Gene Structure

Jitrapakdee¹,

Booker²,

Cassady³

et al. 1997

Journal of Biological Chemistry

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Section: Organization Of the Coding Exons-mentioning

confidence: 81%

Section: Organization Of the Coding Exons-mentioning

confidence: 99%

The Rat Pyruvate Carboxylase Gene Structure

Jitrapakdee¹,

Booker²,

Cassady³

et al. 1997

Journal of Biological Chemistry

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“…The anti-SREBP1a [the N-terminal domain of SREBP (amino acids 1-520)] and the anti-Sp-1 antibodies were purchased from Santa Cruz Biotechnology, and the anti-NF-Ya antibodies were purchased from PharMingen. The sources of all the other chemicals, radioactive materials, and DNA-modifying enzymes were as described (33,34). The oligonucleotides were purchased from Integrated DNA Technologies (Coralville, IA).…”

Section: Methodsmentioning

confidence: 99%

“…The human FAS promoter I-luciferase plasmids LC9-2, LC9-3, LC9-4, LC9-5, and LC11 and the TK-luciferase plasmids TK-272͞-67 and TK-272͞-40 were constructed as described (33,34). LC9-2͞del was generated by deleting the SmaI fragment (nucleotides Ϫ110 to Ϫ40) from LC9 -2.…”

Section: Methodsmentioning

confidence: 99%

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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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Transcription regulatory elements of the first intron control human transglutaminase type I gene expression in epidermal keratinocytes

et al. 1999

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Expression of the transglutaminase type1 gene (TGM1), which encodes an epithelial cell-specific protein cross-linking enzyme, is limited to particular stages of epidermal development and keratinocyte differentiation. As a result, transglutaminase type 1 (TGase1) enzyme activity in epidermal cells increases with the onset of keratinization in vivo and in vitro. We determined, by functional mapping of deletion mutations in the TGM1 5' untranslated region, that an element in first intron of the human TGM1 gene, in addition to the 5' proximal promoter, initiates transcription and upregulates transcriptional activity. These two transcription control elements function interdependently to regulate the expression of the human TGM1 gene in keratinocytes. We also identified distinct regulatory elements that cooperatively modify the 5' proximal and intron 1 promoter activities in response to environmental variations in retinoic acid and calcium ion concentrations. In conclusion, we report that TGM1 differential gene expression is controlled by two distinct elements, proximal and intronic, which function cooperatively to initiate and modulate TGM1 gene transcription in response to regulatory signals. We propose that in nonexpressing cells these regulatory signals repress a default mechanism that operates in their absence. The specificity of their function is integrated into the default mechanism and consists of the tissue-, developmental-, and differentiation-specific interplay of 5' URR and intron 1 elements tuned to physiological status.

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Human Fatty-acid Synthase Gene

Cited by 46 publications

References 45 publications

The Rat Pyruvate Carboxylase Gene Structure

The Rat Pyruvate Carboxylase Gene Structure

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

Transcription regulatory elements of the first intron control human transglutaminase type I gene expression in epidermal keratinocytes

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