scholarly journals Molecular cloning of the mammalian fatty acid synthase gene and identification of the promoter region

1990 ◽  
Vol 271 (3) ◽  
pp. 675-679 ◽  
Author(s):  
C M Amy ◽  
B Williams-Ahlf ◽  
J Naggert ◽  
S Smith
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Single Copy ◽  
Translation Start Site ◽  
S1 Nuclease ◽  
First Intron ◽  
Translation Start ◽  
Sequence Elements ◽  
Flanking Region ◽  
Fatty Acid Synthase Gene

Rat genomic clones encompassing the entire fatty acid synthase gene have been isolated and characterized. The gene is present in a single copy of approx. 20 kb. Genomic DNA sequencing, direct RNA sequencing and S1 nuclease analysis showed that transcription is initiated primarily 1274 nucleotides upstream from the translation start site and that the 87-nucleotide-long 5′-untranslated mRNA sequence is the same in liver, lung and mammary gland. The 5′-flanking region and first intron contain several sequence elements which may be involved in the transcriptional regulation of this gene.

scholarly journals Regulatory elements in the first intron of the rat fatty acid synthase gene

1997 ◽  
Vol 324 (1) ◽  
pp. 113-121 ◽  
Author(s):  
Babak OSKOUIAN ◽  
Vangipuram S. RANGAN ◽  
Stuart SMITH
Keyword(s):  
Fatty Acid ◽  
Binding Site ◽  
Fatty Acid Synthase ◽  
Regulatory Element ◽  
Simian Virus 40 ◽  
Regulatory Elements ◽  
Dominant Negative ◽  
Dependent Manner ◽  
First Intron ◽  
Sequence Elements

Sequence elements have been identified within the 1.2 kb-long first intron of the fatty acid synthase (FAS) gene that mediate both positive and negative effects on transcription. The negative regulatory element, when positioned downstream of either the FAS or simian virus 40 promoter, down-regulates the expression of a coupled reporter gene in an orientation-dependent manner. Sequences mediating this effect have been mapped, by deletion mutagenesis, to two regions approximately within nucleotides +405 to +768 and +924 to +1083. Both regions contain sequence elements that are strongly protected from DNase I digestion by nuclear extracts prepared from liver, but not by those prepared from spleen. The results of run-on assays performed with nuclei derived from tissues that express FAS at either high or low levels indicate that the different rates of transcription of the endogenous FAS gene result from differences in the extent of initiation, so it is unlikely that the negative effect is caused by transcriptional pausing in the first intron. The positive element maps to nt +292 to +297 and corresponds to an authentic binding site for upstream stimulatory factor (USF). This USF-binding element can up-regulate transcription from a heterologous promoter in a position- and orientation-independent manner. However, in the context of the entire FAS first intron, the effect of the USF-binding site is masked unless the effect of the negative elements is ablated by mutagenesis. These results suggest that the dominant negative element of the first intron may play a role in determining the tissue-specific expression of the FAS gene.

Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: interaction with insulin

2000 ◽  
Vol 3 (3) ◽  
pp. 157-162 ◽  
Author(s):  
KATE J. CLAYCOMBE ◽  
YANXIN WANG ◽  
BRYNN H. JONES ◽  
SUYEON KIM ◽  
WILLIAM O. WILKISON ◽  
...  
Keyword(s):  
Transcriptional Regulation ◽  
Fatty Acid ◽  
Gene Transcription ◽  
Fatty Acid Synthase ◽  
Fusion Gene ◽  
Ectopic Expression ◽  
Fold Increase ◽  
Transcriptional Level ◽  
Additive Effects ◽  
Fatty Acid Synthase Gene

Claycombe, Kate J., Yanxin Wang, Brynn H. Jones, Suyeon Kim, William O. Wilkison, Michael B. Zemel, Joseph Chun, and Naima Moustaid-Moussa. Transcriptional regulation of the adipocyte fatty acid synthase gene by agouti: interaction with insulin. Physiol Genomics 3: 157–162, 2000.—Mice carrying dominant mutations at the agouti locus exhibit ectopic expression of agouti gene transcripts, obesity, and type II diabetes through unknown mechanisms. To gain insight into the role of agouti protein in modulating adiposity, we investigated regulation of a key lipogenic gene, fatty acid synthase (FAS) by agouti alone and in combination with insulin. Both agouti and insulin increase FAS activity in 3T3-L1 and in human adipocytes. Agouti and insulin independently and additively increase FAS activity in 3T3-L1 adipocytes. We further investigated the mechanism responsible for the agouti-induced FAS expression in these cells and demonstrated that both insulin (3-fold increase) and agouti (2-fold) increased FAS gene expression at the transcriptional level. Furthermore, insulin and agouti together exerted additive effects (5-fold increase) on FAS gene transcription. Transfection assays of FAS promoter-luciferase fusion gene constructs into 3T3-L1 adipocytes indicated that the agouti response element(s) is (are) located in the −435 to −415 region (−435/−415) of the FAS promoter. Nuclear proteins binding to this novel sequence are adipocyte specific. Thus the agouti response sequences mapped to a region upstream of the insulin-responsive element (which we previously reported to be located at −67/−52), consistent with additive effects of these two factors on FAS gene transcription.

Involvement of Liver X Receptor Alpha in Histone Modifications Across the Target Fatty Acid Synthase Gene

Lipids ◽  
2011 ◽  
Vol 47 (3) ◽  
pp. 249-257 ◽  
Author(s):  
Huihong Yu ◽  
Jinfeng Wu ◽  
Mei Yang ◽  
Jinjun Guo ◽  
Lili Zheng ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Histone Modifications ◽  
Fatty Acid Synthase ◽  
Liver X Receptor ◽  
Receptor Alpha ◽  
Liver X Receptor Alpha ◽  
Fatty Acid Synthase Gene

Transcription factors acting on the promoter of the fatty acid synthase gene

2002 ◽  
Vol 30 (5) ◽  
pp. A102-A102
Author(s):  
M. Schweizer ◽  
K. Roder ◽  
L. Zhang ◽  
S.S. Wolf
Keyword(s):  
Transcription Factors ◽  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Synthase Gene
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