A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo - PubMed (original) (raw)
A fat-specific enhancer is the primary determinant of gene expression for adipocyte P2 in vivo
S R Ross et al. Proc Natl Acad Sci U S A. 1990 Dec.
Abstract
The murine gene for adipocyte P2 encodes an adipocyte-specific member of the family of intracellular lipid binding proteins. The region upstream from the start of transcription of this gene has been found to contain binding sites for the transcription factors c-jun/c-fos and C/EBP (CCAAT/enhancer binding protein) and several short sequence elements found in other adipocyte gene promoters, termed fat-specific elements. To identify DNA sequences that were responsible for the high level of transcription of the gene for adipocyte P2 in vivo, we made a series of transgenic mice containing 168 base pairs (bp), 247 bp, 1.7 kilobases (kb), and 5.4 kb of 5' flanking sequence linked to the bacterial gene chloramphenicol acetyltransferase. Although plasmids containing only 168 bp of 5' sequence including the C/EBP and AP-1 (activation protein 1) binding sites were expressed well in cultured adipocytes, high levels of chloramphenicol acetyltransferase activity in the adipose tissue of transgenic mice were not observed until the 5' flanking region was extended to kb -54. An enhancer mapping between kb -4.9 and kb -5.4 upstream from the start of transcription was identified by transfection of further deletions into cultured adipocytes. This enhancer, when linked to a bp -63 promoter fragment from the gene for adipocyte P2, directed very high level chloramphenicol acetyltransferase expression specifically to adipose tissue in transgenic mice. These results identify a functional adipose-specific enhancer and indicate that it is the major determinant of tissue specificity of the gene for adipocyte P2. These results also demonstrate that the proximal-promoter binding sites for AP-1 and C/EBP are not sufficient or necessary to give adipose-tissue-specific expression in vivo, though they may play an important role in the response of this promoter to glucocorticoids.
Similar articles
- Identification of a fat cell enhancer: analysis of requirements for adipose tissue-specific gene expression.
Graves RA, Tontonoz P, Platt KA, Ross SR, Spiegelman BM. Graves RA, et al. J Cell Biochem. 1992 Jul;49(3):219-24. doi: 10.1002/jcb.240490303. J Cell Biochem. 1992. PMID: 1644859 Review. - Identification of a potent adipocyte-specific enhancer: involvement of an NF-1-like factor.
Graves RA, Tontonoz P, Ross SR, Spiegelman BM. Graves RA, et al. Genes Dev. 1991 Mar;5(3):428-37. doi: 10.1101/gad.5.3.428. Genes Dev. 1991. PMID: 2001842 - A direct role for C/EBP and the AP-I-binding site in gene expression linked to adipocyte differentiation.
Herrera R, Ro HS, Robinson GS, Xanthopoulos KG, Spiegelman BM. Herrera R, et al. Mol Cell Biol. 1989 Dec;9(12):5331-9. doi: 10.1128/mcb.9.12.5331-5339.1989. Mol Cell Biol. 1989. PMID: 2511432 Free PMC article. - mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer.
Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM. Tontonoz P, et al. Genes Dev. 1994 May 15;8(10):1224-34. doi: 10.1101/gad.8.10.1224. Genes Dev. 1994. PMID: 7926726 - [Regulation mechanism of specific expression of tumor marker gene during carcinogenesis].
Imagawa M. Imagawa M. Yakugaku Zasshi. 1996 Jul;116(7):505-18. doi: 10.1248/yakushi1947.116.7_505. Yakugaku Zasshi. 1996. PMID: 8831256 Review. Japanese.
Cited by
- An intronic enhancer of Cebpa regulates adipocyte differentiation and adipose tissue development via long-range loop formation.
Li X, Zeng S, Chen L, Zhang Y, Li X, Zhang B, Su D, Du Q, Zhang J, Wang H, Zhong Z, Zhang J, Li P, Jiang A, Long K, Li M, Ge L. Li X, et al. Cell Prolif. 2024 Mar;57(3):e13552. doi: 10.1111/cpr.13552. Epub 2023 Oct 31. Cell Prolif. 2024. PMID: 37905345 Free PMC article. - Heat-Killed Enterococcus faecalis Prevents Adipogenesis and High Fat Diet-Induced Obesity by Inhibition of Lipid Accumulation through Inhibiting C/EBP-α and PPAR-γ in the Insulin Signaling Pathway.
Lee JH, Woo KJ, Kim MA, Hong J, Kim J, Kim SH, Han KI, Iwasa M, Kim TJ. Lee JH, et al. Nutrients. 2022 Mar 20;14(6):1308. doi: 10.3390/nu14061308. Nutrients. 2022. PMID: 35334965 Free PMC article. - Lysyl oxidase inhibition enhances browning of white adipose tissue and adaptive thermogenesis.
Xing C, Jiang D, Liu Y, Tang Q, Huang H. Xing C, et al. Genes Dis. 2020 Oct 10;9(1):140-150. doi: 10.1016/j.gendis.2020.10.001. eCollection 2022 Jan. Genes Dis. 2020. PMID: 35005114 Free PMC article. - Independent and Distinct Associations of FABP4 and FABP5 With Metabolic Parameters in Type 2 Diabetes Mellitus.
Furuhashi M, Sakuma I, Morimoto T, Higashiura Y, Sakai A, Matsumoto M, Sakuma M, Shimabukuro M, Nomiyama T, Arasaki O, Node K, Ueda S. Furuhashi M, et al. Front Endocrinol (Lausanne). 2020 Sep 23;11:575557. doi: 10.3389/fendo.2020.575557. eCollection 2020. Front Endocrinol (Lausanne). 2020. PMID: 33071982 Free PMC article. Clinical Trial. - C-reactive protein derived from perivascular adipose tissue accelerates injury-induced neointimal hyperplasia.
Chen JY, Zhu XL, Liu WH, Xie Y, Zhang HF, Wang X, Ying R, Chen ZT, Wu MX, Qiu Q, Wang JF, Chen YX. Chen JY, et al. J Transl Med. 2020 Feb 11;18(1):68. doi: 10.1186/s12967-020-02226-x. J Transl Med. 2020. PMID: 32046736 Free PMC article.
References
- Biochemistry. 1979 Nov 27;18(24):5294-9 - PubMed
- Genes Dev. 1989 Dec;3(12B):2021-4 - PubMed
- Nucleic Acids Res. 1984 Jul 25;12(14):5707-17 - PubMed
- Proc Natl Acad Sci U S A. 1984 Sep;81(17):5468-72 - PubMed
- Nucleic Acids Res. 1984 Sep 25;12(18):7035-56 - PubMed
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Other Literature Sources
Research Materials
Miscellaneous