Cig30 and Pitx3 Genes Are Arranged in a Partially Overlapping Tail-to-Tail Array Resulting in Complementary Transcripts

Tvrdík, Petr; Asadi, Abolfazl; Kozak, Leslie P.; Nuglozeh, Edem; Parente, Fabienne; Nedergaard, Jan; Jacobsson, Anders

doi:10.1074/jbc.274.37.26387

Cited by 10 publications

(7 citation statements)

References 25 publications

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“…Seven ELOVL members have been identified in mice and humans, each having a respective gene locus, a unique tissue specific expression pattern with overlapping substrate specificity [5][6][7][8]. Saturated and monounsaturated FAs are preferred substrates of ELOVL1, ELOVL3 and ELOVL6 [8][9][10][11], whereas ELOVL2, ELOVL4 and ELOVL5 use polyunsaturated fatty acids (PUFAs) primarily [10,12,13].…”

Section: Introductionmentioning

confidence: 99%

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

2007

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Elongation of very long-chain fatty acids (ELOVL) members were overexpressed in two preadipocyte cell lines, ELOVL2 and ELOVL3 in 3T3-L1 cells, and ELOVL1-3 in F442A cells. Cells overexpressing ELOVL2, whose preferred substrates are arachidonic acid (AA, C20:4nÀ6) and eicosapentaenoic acid (EPA, C20:5nÀ3), showed an enhanced triacylglycerol (TAG) synthesis and subsequent accumulation of lipid droplets. Incorporation of fatty acid (FA) but not of glucose into TAG was enhanced by ELOVL2-overexpression. Two lipogenic genes encoding diacylglycerol acyltransferase-2 (DGAT2) and fatty acid-binding protein-4 (FABP4, aP2) were induced in ELOVL2-overexpressing cells, whereas no such effect was seen on the fatty acid synthase (FAS) gene.

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Section: Introductionmentioning

confidence: 99%

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

2007

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“…Gene Targeting Construct-A genomic liver DNA library from mouse strain 129/Sv cloned into the Lambda FIXII vector was used to isolate a DNA fragment containing the entire Elovl3 gene (15). A 2.75-kb fragment between SacI and SalI upstream of the first exon was subcloned into the polylinker of the pBluescript SK plasmid in order to become the left arm (LA) in the Elovl3 gene targeting construct (Fig.…”

Section: Elovl3mentioning

confidence: 99%

Role for ELOVL3 and Fatty Acid Chain Length in Development of Hair and Skin Function

Westerberg

Tvrdík

Undén

et al. 2004

Journal of Biological Chemistry

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Very little is known about the in vivo regulation of mammalian fatty acid chain elongation enzymes as well as the role of specific fatty acid chain length in cellular responses and developmental processes. Here, we report that the Elovl3 gene product, which belongs to a highly conserved family of microsomal enzymes involved in the formation of very long chain fatty acids, revealed a distinct expression in the skin that was restricted to the sebaceous glands and the epithelial cells of the hair follicles. By disruption of the Elovl3 gene by homologous recombination in mouse, we show that ELOVL3 participates in the formation of specific neutral lipids that are necessary for the function of the skin. The Elovl3-ablated mice displayed a sparse hair coat, the pilosebaceous system was hyperplastic, and the hair lipid content was disturbed with exceptionally high levels of eicosenoic acid (20:1). This was most prominent within the triglyceride fraction where fatty acids longer than 20 carbon atoms were almost undetectable. A functional consequence of this is that Elovl3-ablated mice exhibited a severe defect in water repulsion and increased trans-epidermal water loss.Fatty acids consisting of up to 16 carbons are synthesized by the well studied fatty acid synthase complex (1). However, a significant amount of the fatty acids produced by fatty acid synthase are further elongated into very long chain fatty acids (VLCFA). 1 VLCFA have been recognized as structural components in a variety of fat molecules such as glycerolipids and sphingolipids. They are found in virtually all cells and are major constituents of the brain, skin, and testis (2-4). Depending on their chain length and degree of unsaturation, they contribute to membrane fluidity and other chemical properties of the cell.Formation of VLCFA is performed in the endoplasmic reticulum, in the early Golgi, and in mitochondria by membranebound enzymes, the former being more prominent (5, 6).Recently, five mammalian genes, Elovl1-5, 2 whose protein products belong to a highly conserved family of microsomal enzymes involved in the formation of VLCFA, have been identified (7-10). All five genes show a diverse tissue-specific expression pattern indicating a unique role for different VLCFA in different cell types.Although the general functions of the Elovl genes are partially understood (8 -14), very little is known about the role of specific fatty acid chain length in cellular responses and developmental processes. The ELOVL3 protein has been suggested to be involved in the formation of saturated and monounsaturated fatty acyl chains containing up to 24 carbon atoms (9). Elovl3 gene expression has only been detected in brown adipose tissue, liver, and skin (7, 9). To assess the in vivo role of ELOVL3, we disrupted the Elovl3 gene by homologous recombination in mouse. Here we describe the characterization of Elovl3 expression in skin and present evidence that ELOVL3 participates in the formation of certain VLCFA and triglycerides in certain cells of the hair follicles and...

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“…The promoter region of the mouse Elovl3 gene was isolated via high-fidelity genomic PCR with primers designed using available genomic sequence information (20). To identify putative DNA consensus regulatory sites, we scanned the z1.1 kb fragment of the Elovl3 region upstream of the translation start site [including a 171 bp long 59 untranslated region (boldface in Fig.…”

Section: Isolation and Functional Characterization Of The Mouse Elovlmentioning

confidence: 99%

Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional status

Anzulovich

Mir

Brewer

et al. 2006

Journal of Lipid Research

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The ELOVL3 protein is a very long-chain fatty acid elongase found in liver, skin, and brown adipose tissues. Circadian expression of the Elovl3 gene in the liver is perturbed in mutant CLOCK mice but persists in mice with severe hepatic dysfunction. A reliance on an intact clock, combined with the refractoriness to liver decompensation and the finding of a robust sexually dimorphic pattern of expression, evince a particularly complex mode of transcriptional control. The Elovl3 gene upstream region was repressed by RevErba and activated by sterol-regulatory element binding protein-1 (SREBP1) transcription factors. We propose that the temporal coordination of RevErba and SREBP1 activities integrates clock and nutrition signals to drive a subset of oscillatory transcripts in the liver. Proteolytic activation of SREBP1 is circadian in the liver, and because the cycle of SREBP1 activation was reversed after restricting meals to the inactive phase of the day, this factor could serve as an acute sensor of nutritional state. SREBP1 regulates many known lipogenic and cholesterogenic circadian genes; hence, our results could explain how feeding can override brain-derived entraining signals in the liver. This mechanism would permit a rapid adjustment in the sequence of key aspects of the absorptive and postabsorptive phases in the liver.-Anzulovich, A., A. Mir, M. Brewer, G. Ferreyra, C. Vinson, and R. Baler. Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional status.

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Cig30 and Pitx3 Genes Are Arranged in a Partially Overlapping Tail-to-Tail Array Resulting in Complementary Transcripts

Cited by 10 publications

References 25 publications

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

ELOVL2 overexpression enhances triacylglycerol synthesis in 3T3‐L1 and F442A cells

Role for ELOVL3 and Fatty Acid Chain Length in Development of Hair and Skin Function

Elovl3: a model gene to dissect homeostatic links between the circadian clock and nutritional status

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