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PATZ1 down-regulates FADS1 by binding to rs174557 and is opposed by SP1/SREBP1c
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- Pan, Gang (author)
- Uppsala universitet,Medicinsk genetik och genomik
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- Ameur, Adam (author)
- Uppsala universitet,Institutionen för immunologi, genetik och patologi
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- Enroth, Stefan, 1976- (author)
- Uppsala universitet,Medicinsk genetik och genomik
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- (creator_code:org_t)
- 2016-12-08
- 2017
- English.
- In: Nucleic Acids Research. - : Oxford University Press (OUP). - 0305-1048 .- 1362-4962. ; 45:5, s. 2408-2422
- Journal article (peer-reviewed)
Abstract
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- The FADS1 and FADS2 genes in the FADS cluster encode the rate-limiting enzymes in the synthesis of long-chain polyunsaturated fatty acids (LC-PUFAs). Genetic variation in this region has been associated with a large number of diseases and traits many of them correlated to differences in metabolism of PUFAs. However, the causative variants leading to these associations have not been identified. Here we find that the multiallelic rs174557 located in an AluYe5 element in intron 1 of FADS1 is functional and lies within a PATZ1 binding site. The derived allele of rs174557, which is the common variant in most populations, diminishes binding of PATZ1, a transcription factor conferring allele-specific downregulation of FADS1 The PATZ1 binding site overlaps with a SP1 site. The competitive binding between the suppressive PATZ1 and the activating complex of SP1 and SREBP1c determines the enhancer activity of this region, which regulates expression of FADS1.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
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