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A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation.

ABSTRACT: The integration of genetic information in the cellular and nuclear environments is crucial for deciphering the way in which the genome functions under different physiological conditions. Experimental techniques of 3D nuclear mapping, a high-flow approach such as transcriptomic data analyses, and statistical methods for the development of co-expressed gene networks, can be combined to develop an integrated approach for depicting the regulation of gene expression. Our work focused more specifically on the mechanisms involved in the transcriptional regulation of genes expressed in muscle during late foetal development in pig. The data generated by a transcriptomic analysis carried out on muscle of foetuses from two extreme genetic lines for birth mortality are used to construct networks of differentially expressed and co-regulated genes. We developed an innovative co-expression networking approach coupling, by means of an iterative process, a new statistical method for graph inference with data of gene spatial co-localization (3D DNA FISH) to construct a robust network grouping co-expressed genes. This enabled us to highlight relevant biological processes related to foetal muscle maturity and to discover unexpected gene associations between IGF2, MYH3 and DLK1/MEG3 in the nuclear space, genes that are up-regulated at this stage of muscle development.

SUBMITTER: Marti-Marimon M

PROVIDER: S-EPMC6033925 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation.

Marti-Marimon M M Vialaneix N N Voillet V V Yerle-Bouissou M M Lahbib-Mansais Y Y Liaubet L L

Scientific reports 20180705 1

The integration of genetic information in the cellular and nuclear environments is crucial for deciphering the way in which the genome functions under different physiological conditions. Experimental techniques of 3D nuclear mapping, a high-flow approach such as transcriptomic data analyses, and statistical methods for the development of co-expressed gene networks, can be combined to develop an integrated approach for depicting the regulation of gene expression. Our work focused more specificall ...[more]

PMID: 29977047

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Project description:Manipulating maternal nutrition during specific periods of gestation can result in re-programming of fetal and post-natal development. In this experiment we investigated how a feed restriction of 85% compared with 140% of total metabolizable energy requirements, fed to cows during mid-to-late gestation, influences phenotypic development of fetuses and mRNA expression of growth (Insulin-Like Growth Factor family and Insulin Receptor (INSR)), myogenic (Myogenic Differentiation 1 (MYOD1), Myogenin (MYOG), Myocyte Enhancer Factor 2A (MEF2A), Serum Response Factor (SRF)) and adipogenic (Peroxisome Proliferator Activated Receptor Gamma (PPARG)) genes in fetal longissimus dorsi (LD) and semitendinosus (ST) muscle. DNA methylation of imprinted genes, Insulin Like Growth Factor 2 (IGF2) and Insulin Like Growth Factor 2 Receptor (IGF2R), and micro RNA (miRNA) expression, were also examined as potential consequences of poor maternal nutrition, but also potential regulators of altered gene expression patterns.While the nutrient restriction impacted dam body weight, no differences were observed in phenotypic fetal measurements (weight, crown-rump length, or thorax circumference). Interestingly, LD and ST muscles responded differently to the differential pre-natal nutrient levels. While LD muscle of restricted fetal calves had greater mRNA abundances for Insulin Like Growth Factor 1 and its receptor (IGF1 and IGF1R), IGF2R, INSR, MYOD1, MYOG, and PPARG, no significant differences were observed for gene expression in ST muscle. Similarly, feed restriction had a greater impact on the methylation level of IGF2 Differentially Methylated Region 2 (DMR2) in LD muscle as compared to ST muscle between treatment groups. A negative correlation existed between IGF2 mRNA expression and IGF2 DMR2 methylation level in both LD and ST muscles. Differential expression of miRNAs 1 and 133a were also detected in LD muscle.Our data suggests that a nutrient restriction of 85% as compared to 140% of total metabolizable energy requirements during the 2nd half of gestation can alter the expression of growth, myogenic and adipogenic genes in fetal muscle without apparent differences in fetal phenotype. It also appears that the impact of feed restriction varies between muscles suggesting a priority for nutrient partitioning depending on muscle function and/or fiber composition. Differences in the methylation level in IGF2, a well-known imprinted gene, as well as differences in miRNA expression, may be functional mechanisms that precede the differences in gene expression observed, and could lead to trans-generational epigenetic programming.

Project description:BACKGROUND:Maternal nutrition has been highlighted as one of the main factors affecting intra-uterine environment. The increase in nutritional requirements by beef cows during late gestation can cause nutritional deficiency in the fetus and impact the fetal regulation of genes associated with myogenesis and immune response. METHODS:Forty days before the expected calving date, cows were assigned to one of two diets: 100% (control) or 70% (restricted group) of the daily energy requirement. Muscle samples were collected from 12 heifers and 12 steers, and blood samples were collected from 12 steers. The objective of this work was to identify and to assess the biological relevance of differentially expressed genes (DEG) in the skeletal muscle and blood of beef calves born from cows that experienced [or not] a 30% energy restriction during the last 40 days of gestation. RESULTS:A total of 160, 164, and 346 DEG (q-value<?0.05) were identified in the skeletal muscle for the effects of diet, sex, and diet-by-sex interaction, respectively. For blood, 452, 1392, and 155 DEG were identified for the effects of diet, time, and diet-by-time interaction, respectively. For skeletal muscle, results based on diet identified genes involved in muscle metabolism. In muscle, from the 10 most DEG down-regulated in the energy-restricted group (REST), we identified 5 genes associated with muscle metabolism and development: SLCO3A1, ATP6V0D1, SLC2A1, GPC4, and RASD2. In blood, among the 10 most DEG, we found genes related to response to stress up-regulated in the REST after weaning, such as SOD3 and INO80D, and to immune response down-regulated in the REST after vaccination, such as OASL, KLRF1, and LOC104968634. CONCLUSION:In conclusion, maternal energy restriction during late gestation may limit the expression of genes in the muscle and increase expression in the blood of calves. In addition, enrichment analysis showed that a short-term maternal energy restriction during pregnancy affects the expression of genes related to energy metabolism and muscle contraction, and immunity and stress response in the blood. Therefore, alterations in the intra-uterine environment can modify prenatal development with lasting consequences to adult life.

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A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation.

Publications

A new approach of gene co-expression network inference reveals significant biological processes involved in porcine muscle development in late gestation.

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