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P53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid receptor in the liver of preweaning piglets.

ABSTRACT: Previous studies indicate that Chinese indigenous pig breeds demonstrate distinct pattern of glucocorticoid receptor (GR) expression, which is associated with their unique growth and metabolic phenotypes. Here we sought to unravel the transcriptional mechanisms underlying the breed-specific hepatic GR expression in preweaning Chinese Erhualian (EHL) and Western Large White (LW) piglets. Total GR mRNA and the predominant GR mRNA variant 1-9/10 were expressed significantly higher in EHL compared with LW piglets (P<0.01), which was associated with more enriched histone H3 acetylation on 1-9/10 promoter (P<0.05). Nuclear content of transcription factor specificity protein 1 (Sp1) was significantly lower in EHL piglets, yet its binding to GR 1-9/10 promoter was significantly higher in EHL piglets, as revealed by chromatin immunoprecipitation assays. Although p53 binding to GR promoter 1-9/10 did not differ between breeds, expression of p53 mRNA and protein, as well as its binding to Sp1, were significantly higher in EHL piglets. Moreover, p53 activator doxorubicin significantly enhanced GR 1-9/10 promoter activity in HepG2 cells at 100 nM, which was associated with significantly higher protein content of p53 and GR. Sp1 inhibitor, mithramycin A, significantly inhibited (P<0.05) the basal activity of GR promoter 1-9/10 and completely blocked doxorubicin -induced activation of GR promoter 1-9/10. These data indicate that higher hepatic GR expression in EHL piglets attributes mainly to the enhanced transcription of GR promoter 1-9/10, which is achieved from breed-specific interaction of p53 and Sp1 on porcine GR 1-9/10 promoter.

SUBMITTER: Zou H

PROVIDER: S-EPMC3737268 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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p53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid receptor in the liver of preweaning piglets.

Zou Huafeng H Jiang Zheng Z Li Runsheng R Jia Yimin Y Yang Xiaojing X Ni Yingdong Y Zhao Ruqian R

PloS one 20130807 8

Previous studies indicate that Chinese indigenous pig breeds demonstrate distinct pattern of glucocorticoid receptor (GR) expression, which is associated with their unique growth and metabolic phenotypes. Here we sought to unravel the transcriptional mechanisms underlying the breed-specific hepatic GR expression in preweaning Chinese Erhualian (EHL) and Western Large White (LW) piglets. Total GR mRNA and the predominant GR mRNA variant 1-9/10 were expressed significantly higher in EHL compared w ...[more]

PMID: 23950944

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Project description:BackgroundRecent increases in intra-litter variability in weaning weight have raised swine production costs. A contributor to this variability is the normal birth weight pig that grows at a slower rate than littermates of similar birth weight. The goal of this study was to interrogate biochemical profiles manifested in skeletal muscle originating from slow growing (SG) and faster growing littermates (control), with the aim of identifying differences in metabolic pathway utilization between skeletal muscle of the SG pig relative to its littermates. Samples of longissimus muscle from littermate pairs of pigs were collected at 21 d of age for metabolomic analysis (Metabolon, Inc., Durham, NC).ResultsBirth weights did not differ between littermate pairs of SG and Control pigs (P > 0.05). Weaning weights differed by 1.51 ± 0.19 kg (P < 0.001). Random forest (RF) analysis was effective at segregating the metabolome of muscle samples by growth rate, resulting in a predictive accuracy of 81% versus random segregation (50%). Decreases in sugars in the pentose phosphate pathway (PPP) in the longissimus of SG pigs were detected (P < 0.05). Decreases were also apparent in glycolytic intermediates (glycerol-3-phosphate and lactate) and key glycolysis-derived intermediates (glucose-6-phosphate and fructose-6-phosphate; P < 0.05). SG pigs had increased levels of phospholipids, lysolipids, diacylglycerols, and sphingolipids (P < 0.05). Pathway analysis identified a cluster of molecules associated with muscle and collagen/extracellular matrix breakdown that are increased in the SG pig (glutamate, 3-methylhistidine and hydroxylated proline moieties; P < 0.05). Nicotinate metabolism was altered in SG pigs, resulting in a 78% decrease in the nicotinamide adenine dinucleotide pool (P < 0.05).ConclusionsThese metabolomic data provide the first evidence for biochemical mechanisms that should be investigated to determine if they have a potential role in the slow growth in some normal birth weight piglets that contribute to increased intra-litter variability in weaning weights and provides essential information and potential targets for the development of nutritional intervention strategies.

Dataset Information

P53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid receptor in the liver of preweaning piglets.

Publications

p53 cooperates with Sp1 to regulate breed-dependent expression of glucocorticoid receptor in the liver of preweaning piglets.

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