共查询到20条相似文献,搜索用时 15 毫秒
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Li-Na Wei 《Biochimica et Biophysica Acta (BBA)/Molecular and Cell Biology of Lipids》2012,1821(1):206-212
Retinoic acid (RA) acts by binding to nuclear RA receptors (RARs) to regulate a broad spectrum of downstream target genes in most cell types examined. In cytoplasm, RA binds specifically to cellular retinoic acid binding proteins I (CRABPI), and II. Although the function of CRABPI in animals remains the subject of debate, it is believed that CRABPI binding facilitates RA metabolism, thereby modulating the concentration of RA and the type of RA metabolites in cells. The basal promoter of the CrabpI gene is a housekeeping promoter that can be regulated by thyroid hormones (T3), DNA methylation, sphinganine, and ethanol acting on its upstream regulatory region. T3 regulation of CrabpI is mediated by the binding of thyroid hormone receptor (TR) to a TR response element (TRE) approximately 1 kb upstream of the basal promoter. Specifically, in the adipocyte differentiation process, T3 regulation is bimodal and closely associated with the cellular differentiation status: T3 activates CrabpI in predifferentiated cells (e.g., mesenchymal precursors or fibroblasts), but suppresses this gene once cells are committed to adipocyte differentiation. These disparate effects are functions of T3-triggered differential recruitment of coregulatory complexes in conjunction with chromatin looping/folding that alters the configuration of this genomic locus along adipocyte differentiation. Subsequent sliding, disassembly and reassembly of nucleosomes occur, resulting in specific changes in the conformation of the basal promoter chromatin at different stages of differentiation. This chapter summarizes studies illustrating the epigenetic regulation of CrabpI expression during adipocyte differentiation. Understanding the pathways regulating CrabpI in this specific context might help to illuminate the physiological role of CRABPI in vivo. This article is part of a special issue entitled: Retinoid and Lipid Metabolism. 相似文献
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Yong-Zhen Huang En-Ping Zhang Jing Wang Yong-Tao Huai Liang Ma Fu-Ying Chen Xian-Yong Lan Chu-Zhao Lei Xing-Tang Fang Ju-Qiang Wang Hong Chen 《Molecular biology reports》2011,38(3):2037-2042
Adipocyte determination and differentiation-dependent factor 1/sterol regulatory element-binding protein-1c (ADD1/SREBP1c) is a major determinant of tissue differential lipogenic capacity in mammalian and avian species. The objectives of the present study were to focus on insertion-deletion polymorphism (indel) in the bovine ADD1/SREBP1c gene, and analyzing its effect on growth traits in a sample of 1035 cattle belonging to four Chinese cattle breeds. PCR-SSCP, DNA sequencing and agarose electrophoresis methods were used. The 778 bp PCR products of ADD1/SREBP1c gene exhibited three genotypes and two alleles were revealed: W and D. Frequencies of the W allele varied from 0.8651 to 1.000. The associations of the 84 bp indel mutation of ADD1/SREBP1c gene with growth traits of 265 Nanyang cows were analyzed. The animals with genotype WD had significantly higher birth weight, body weight, average daily gain than those with genotype WW at birth, 6-, 12-, 18-, and 24-month old (P < 0.05 or P < 0.01). These results suggest that the indel mutation of bovine ADD1/SREBP1c gene may influence the growth traits in cattle. 相似文献
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Promoter-specific roles for liver X receptor/corepressor complexes in the regulation of ABCA1 and SREBP1 gene expression 总被引:7,自引:0,他引:7 下载免费PDF全文
Wagner BL Valledor AF Shao G Daige CL Bischoff ED Petrowski M Jepsen K Baek SH Heyman RA Rosenfeld MG Schulman IG Glass CK 《Molecular and cellular biology》2003,23(16):5780-5789
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Wei LN 《Biochimica et biophysica acta》2012,1821(1):206-212
Retinoic acid (RA) acts by binding to nuclear RA receptors (RARs) to regulate a broad spectrum of downstream target genes in most cell types examined. In cytoplasm, RA binds specifically to cellular retinoic acid binding proteins I (CRABPI), and II. Although the function of CRABPI in animals remains the subject of debate, it is believed that CRABPI binding facilitates RA metabolism, thereby modulating the concentration of RA and the type of RA metabolites in cells. The basal promoter of the CrabpI gene is a housekeeping promoter that can be regulated by thyroid hormones (T3), DNA methylation, sphinganine, and ethanol acting on its upstream regulatory region. T3 regulation of CrabpI is mediated by the binding of thyroid hormone receptor (TR) to a TR response element (TRE) approximately 1 kb upstream of the basal promoter. Specifically, in the adipocyte differentiation process, T3 regulation is bimodal and closely associated with the cellular differentiation status: T3 activates CrabpI in predifferentiated cells (e.g., mesenchymal precursors or fibroblasts), but suppresses this gene once cells are committed to adipocyte differentiation. These disparate effects are functions of T3-triggered differential recruitment of coregulatory complexes in conjunction with chromatin looping/folding that alters the configuration of this genomic locus along adipocyte differentiation. Subsequent sliding, disassembly and reassembly of nucleosomes occur, resulting in specific changes in the conformation of the basal promoter chromatin at different stages of differentiation. This chapter summarizes studies illustrating the epigenetic regulation of CrabpI expression during adipocyte differentiation. Understanding the pathways regulating CrabpI in this specific context might help to illuminate the physiological role of CRABPI in vivo. This article is part of a special issue entitled: Retinoid and Lipid Metabolism. 相似文献
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Motoharu Awazawa Kohjiro Ueki Kazunori Inabe Kazuma Kaneko Nabeel Bardeesy Ryozo Nagai 《Biochemical and biophysical research communications》2009,382(1):51-2811
Adiponectin, one of the insulin-sensitizing adipokines, has been shown to activate fatty acid oxidation in liver and skeletal muscle, thus maintaining insulin sensitivity. However, the precise roles of adiponectin in fatty acid synthesis are poorly understood. Here we show that adiponectin administration acutely suppresses expression of sterol regulatory element-binding protein (SREBP) 1c, the master regulator which controls and upregulates the enzymes involved in fatty acid synthesis, in the liver of +Leprdb/+Leprdb (db/db) mouse as well as in cultured hepatocytes. We also show that adiponectin suppresses SREBP1c by AdipoR1, one of the functional receptors for adiponetin, and furthermore that suppressing either AMP-activated protein kinase (AMPK) via its upstream kinase LKB1 deletion cancels the negative effect of adiponectin on SREBP1c expression. These data show that adiponectin suppresses SREBP1c through the AdipoR1/LKB1/AMPK pathway, and suggest a possible role for adiponectin in the regulation of hepatic fatty acid synthesis. 相似文献
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Weinhofer I Kunze M Rampler H Bookout AL Forss-Petter S Berger J 《The Journal of biological chemistry》2005,280(50):41243-41251
The peroxisomal ATP binding cassette (ABC) transporter adrenoleukodystrophy-related protein, encoded by ABCD2, displays functional redundancy with the X-linked adrenoleukodystrophy-associated protein, making ABCD2 up-regulation of therapeutic value. Cholesterol lowering activates human ABCD2 in cultured cells. To investigate in vivo regulation by sterols, we first characterized a sterol regulatory element (SRE) in the murine Abcd2 promoter that is directly bound by SRE-binding proteins (SREBPs). Intriguingly, this element overlaps with a direct repeat 4, which serves as binding site for liver X receptor (LXR)/retinoid X receptor heterodimers, suggesting novel cross-talk between SREBP and LXR/retinoid X receptor in gene regulation. Using fasting-refeeding and cholesterol loading, SREBP accessibility to the SRE/direct repeat 4 was tested. Results suggest that adipose Abcd2 is induced by SREBP1c, whereas hepatic Abcd2 expression is down-regulated by concurrent activation of LXRalpha and SREBP1c. In cell culture, SREBP1c-mediated Abcd2 induction is counteracted by ligand-activated LXRalpha. Finally, hepatic Abcd2 expression in LXRalpha,beta-deficient mice is inducible to levels vastly exceeding wild type. Together, we identify LXRalpha as negative modulator of Abcd2, acting through a novel regulatory mechanism involving overlapping SREBP and LXRalpha binding sites. 相似文献
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Ghirlando R Giles K Gowher H Xiao T Xu Z Yao H Felsenfeld G 《Biochimica et biophysica acta》2012,1819(7):644-651
The DNA sequence elements called insulators have two basic kinds of properties. Barrier elements block the propagation of heterochromatic structures into adjacent euchromatin. Enhancer blocking elements interfere with interaction between an enhancer and promoter when placed between them. We have dissected a compound insulator element found at the 5' end of the chicken β-globin locus, which possesses both activities. Barrier insulation is mediated by two kinds of DNA binding proteins: USF1/USF2, a heterodimer which recruits multiple enzyme complexes capable of marking histone on adjacent nucleosomes with 'activating' marks, and Vezf1, which protects against DNA methylation. We have found that the heterochromatic region upstream of the insulator element is maintained in its silent state by a dicer-dependent mechanism, suggesting a mechanism for Vezf1 function in the insulator. Enhancer blocking function in the β-globin insulator element is conferred by a binding site for CTCF. Consistent with this property, CTCF binding was found some years ago to be essential for imprinted expression at the Igf2/H19 locus. Work in many laboratories has since demonstrated that CTCF helps stabilize long-range interactions in the nucleus. We have recently shown that in the case of the human insulin locus such an interaction, over a distance of ~300kb, can result in stimulation of a target gene which itself is important for insulin secretion. This article is part of a Special Issue entitled: Chromatin in time and space. 相似文献
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Kimura K Tawara S Igarashi K Takenaka A 《Bioscience, biotechnology, and biochemistry》2007,71(1):16-22
Oxidative stress is recognized to be associated with the development of insulin resistance. Although free radicals are generated in various ways in vivo, very few radical generators have been used to investigate the effect of oxidative stress on cellular insulin signaling. In order to compare the effect of radical generators with different sites and durations of radical formation on liver insulin action, primary cultured rat hepatocytes were incubated with radical generators and insulin-dependent regulation of gene expression was examined. The hydrophobic 2,2'-azobis(2,4-dimethylvaleronitrile) (AMVN) radical and H2O2 increased plasma membrane damage, and the hydrophilic 2-2'-azobis(2-amidinopropane) dihydrochloride (AAPH) radical and buthionine sulfoxyimine (BSO) increased oxidation of intracellular substances. Paraquat (PQ) and H2O2 inhibited insulin-dependent repression of insulin-like growth factor-binding protein-1 (IGFBP-1) and phosphoenolpyruvate carboxykinase (PEPCK) gene expression. These results indicate that PQ and H2O2 impair insulin action effectively and are suitable for examining crosstalk between oxidative stress and insulin signaling in liver-cell culture systems. 相似文献
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Elisabetta Morini Dadi Gao Emily M.Logan Monica Salani Aram J.Krauson Anil Chekuri Yei-Tsung Chen Ashok Ragavendran Probir Chakravarty Serkan Erdin Alexei Stortchevoi Jesper Q.Svejstrup Michael E.Talkowski Susan A.Slaugenhaupt 《遗传学报》2022,49(7):654-665
Familial dysautonomia(FD), a hereditary sensory and autonomic neuropathy, is caused by a mutation in the Elongator complex protein 1(ELP1) gene that leads to a tissue-specific reduction of ELP1 protein. Our work to generate a phenotypic mouse model for FD headed to the discovery that homozygous deletion of the mouse Elp1 gene leads to embryonic lethality prior to mid-gestation. Given that FD is caused by a reduction, not loss, of ELP1, we generated two new mouse models by introducing different c... 相似文献