|Cushman, Robert - Bob|
Submitted to: International Society for Animal Genetics (ISAG)
Publication Type: Abstract Only
Publication Acceptance Date: 3/16/2017
Publication Date: N/A
Citation: N/A Interpretive Summary:
Technical Abstract: During the first 50 d of gestation, organogenesis is taking place. Nutritional influences during this time may alter the mammalian phenotype through affecting gene regulatory mechanisms, thus “programming” potential susceptibilities to chronic disease and metabolic issues into the animal’s genome. We tested the hypothesis that maternal nutrition during the first 50 d of gestation would alter the transcriptome of histones and histone related genes in the developing fetal liver. Fourteen beef heifers were estrus synchronized and assigned to 2 dietary treatments at breeding (CON-100% of nutrient requirements to gain 0.45kg/d; RES-60% of CON). Heifers were ovariohysterectomized on d 50 of gestation and fetal livers were dissected, flash frozen, and RNA extracted. RNA-seq analysis was conducted on the Illumina HiSeq 2500 platform using 50-bp paired-end reads at a depth of 2 x 10.4M reads/sample. Transcriptome analysis was performed in collaboration with USDA-ARS-MARC using the Tuxedo Suite, and KEGG pathways were analyzed with DAVID 6.8. A total of 548 genes (P < 0.01) were used for ontological analysis, of which 201 were false discovery rate protected (q < 0.10). We found 9 histones that were upregulated in RES vs. CON including members of the histone H1, H2A, H2B, and H4 families. The 13 differentially expressed histone modifying transcripts included genes associated with acetylation and de-acetylation, methylation, phosphorylation, and ubiquitination. Of particular note, HDAC10 was 2.67- fold greater (q < 0.05) in liver of RES fetuses. Additionally, the histone deacetylase complex gene, CIR1 was 2.22-fold greater (q < 0.05) in RES. Only one gene associated with histone modifications, SET was 1.77- fold lower (P = 0.006; q = 0.16) in RES. The SET gene is involved in preventing H4 lysine acetylation. Thus, a moderate nutrient restriction during the first 50 d of gestation alters the expression of histone and histone modifying genes in the bovine fetal liver. This implies that early maternal nutrition initiates developmental programming through epigenetic remodeling.