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Title:Longitudinal gene networks, canonical pathways and functional analysis of microarray data from Longissimus thoracis et lumborum muscle samples of early-weaned Angus steers
Author(s):Moisa, Sonia
Advisor(s):Loor, Juan J.
Department / Program:Animal Sciences
Discipline:Animal Sciences
Degree Granting Institution:University of Illinois at Urbana-Champaign
systems biology
gene expression
adipocyte differentiation
Abstract:Metabolic regulation in complex organisms relies partly on transcriptional control of gene networks as a long-term mechanism affecting the level of expression of several key enzymes. Objectives were to evaluate temporal gene expression profiles in Longissimus thoracis et lumborum of early-weaned (155 +/- 10 d age at weaning) Angus steers (n = 7/diet) fed a high-starch (HiS, NEG = 5.98 MJ/kg diet dry matter) or low-starch (LoS, NEG = 4.97 MJ/kg) diet for 120 d, at which point all steers were switched to a common feedlot diet until slaughter. Muscle samples biopsies for transcript profiling were collected at 0, 60, 120, and 220 d of feeding. A 13,153 bovine oligonucleotide (70-mers) array was used for transcript profiling. Canonical pathways analysis was performed by means of the Kyoto Encyclopedia of Genes and Genomes (KEGG) and functional analysis was performed by the Database for Annotation, Visualization and Integrated Discovery (DAVID) bioinformatics software’s. ANOVA using a false discovery rate < 0.01 revealed ca. 4,300 differentially expressed genes (DEG) due to time. During the growing phase, the most prominent differences occurred at 60 vs. 0 days when a total of 1,934 DEG were observed. The number of DEG due to time, however, was 4,032 at 220 vs. 0 days. Pentose and glucuronate interconversions, Sulfur Metabolism, Steroid biosynthesis and PPAR Signaling Pathway were the most recurrent KEGG significant pathways for this microarray analysis. KEGG pathway results were in accordance with the metabolic processes that were expected to happen during the growing and finishing periods. DAVID significant lipid-related biological processes highlighted a lack in LDL receptors during the growing phase. Steroid synthesis could be used as a sign of production of LDL that contain cholesterol; moreover, the upregulation of the carnitine shuttle and the biosynthesis of acylglycerols also are signals for lipogenesis during the finishing phase. DAVID gene expression-related most impacted biological process was the circadian regulation of gene expression. Genes that showed significant expression are evidence for genetic-related regulation of feed intake mainly during the finishing phase period. A second study was conducted to test the effect of early weaning (EW) (140 ± 6 days after birth) compared to steers that were normal weaned (218 ± 6 days after birth) with corn-based creep supplement (NW), and normal weaning with no creep feeding (CON). In this study, a transcription regulators analysis was performed. As a result, Yin Yang 1 (YY1) was the transcription regulator that affected the greatest number of molecules (126 genes). Within these affected genes with direct and indirect connection to YY1 gene, Insulin Growth Factor Binding Protein 5 (IGFBP5), Signal transducer and activator of transcription 5B (STAT5B), General Transcription Factor 2B (GTF2B), and K(lysine) acetyltransferase 2B (KAT2B), were the genes which showed to have a role on myogenesis and adipocyte differentiation. The outcome of this study was that the administration of starch in the diet of early weaned steers early in life, was expressed in higher scores for intramuscular fat deposition compared with normal weaned steers that received and did not receive creep feeding. Although, there was not a direct effect of YY1 as a regulator of adipocyte differentiation, there were indirect effects by means of YY1 target genes. IGFBP5 which is both PPAR- and VDR- target gene presented a role as an enhancer of adipocyte differentiation. This was noticeable in early weaned steers by IGFBP5 expression that enhanced the release of IGF-1 which stimulates adipocyte differentiation. Results revealed marked adaptations in networks and pathways during rapid growth of skeletal muscle.  
Issue Date:2012-02-01
Genre:Dissertation / Thesis
Rights Information:Copyright 2011 Sonia Moisa
Date Available in IDEALS:2014-02-01
Date Deposited:2011-12

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