Progress 01/01/07 to 12/31/09
Outputs
OUTPUTS: The recent technologies that have led to the new field of functional genomics (how the genome of an organism regulates homeostasis and responds to stimuli) are providing a clearer understanding of how organisms interact with their environment and in particular their diet. We are beginning to learn how the diet may have long-term influence on performance and health. A form of epigenetic regulation has been recently described called fetal "programming". Fueled by epidemiological data the "fetal origins" hypothesis suggests that a poor in utero environment resulting from maternal dietary or placental insufficiency may "program" susceptibility in the fetus to cardiovascular or metabolic disorders. We have observed similar apparent programming by dietary manipulation in the chicken. When birds are challenged with a diet low in phosphorus (P) for 90 hours post-hatch they obtain the ability to better utilize P later in life. This increased retention of P from the diet can partially be explained by an enduring increase in the expression of the intestine-specific Na/P cotransporter (NaPcoT) gene during programming as well as later in life when fed P restricted diets. The resulting data provide the first evidence for neonatal programming of gene expression in an oviparous species. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Broilers fed the moderately deficient diet (L) to 90 hr were better able to handle a deficiency in P in the grower/finisher phase (22 to 38 d of age than those fed a control diet in the first 90 hr. Not only were the broilers fed the L diet early on heavier at 38 days of age, but they were more efficient in converting feed to gain, had high tibia ash and higher P retention than those fed the C diet in the first 90 hr of life. This clearly establishes that imprinting or modifications are occurring in the animal that are long term and that allow for improved P utilization when P deficient diets are fed in the grower/finisher phases. The reduction of P in the post hatch diet had a significant effect on the expression of the NaPcoT by stimulating an average 2.8-fold increase in the mRNA levels in the small intestine. Nearly identical stimulatory effects were seen across all segments of the intestine with relative expression decreasing from duodenum to ileum. This pattern is similar to that in trout where a 2 fold induction of the NaPcoT was observed as a result of a 40% reduction of diet P (Sugiura et al, 2003). This is also in the range of the induction of expression of the NaPcoT as a result of feeding a low P diet in mice (Segawa et al, 2004). The effect of reducing P from a control diet level of 0.5% P to a low P diet level of 0.25% P induced NaPcoT expression an average of 2.3 fold. Apparent methylation was observed at 29 positions within the 52 predicted CpGs in the PCR products produced in the control samples for NaPcoT. As a comparison only 19 CpGs were methylated in the DNAs extracted from the neonatally programmed duodenums. This 43% reduction in methylation of cytosines in this region may be involved in the increased gene expression observed in the programmed birds relative to controls. Further characterization of the differential methylation patterns is needed both post programming as well as later in life to verify these observations. This data along with the other preliminary data demonstrating long term effects on performance and gene expression as a result of nutritional neonatal programming in the chick are strong evidence for the role of epigenetics in the regulation of these phenomena. Further work must be conducted to elucidate the specifics of neonatal programming in the chicken, the extent of its effects on DNA methylation of the NaPcoT as well as other genes. Demonstrating these epigenetic effects in the chicken will provide both a significant contribution the understanding of the regulation of genomes, particularly in oviparous species but also provide a potential mechanism for improving performance and the economics of poultry production.
Publications
- Angel, R., Ashwell, C.M. (2008) Dietary conditioning results in improved phosphorus utilization. Proceedings of the XXIII World Poultry Congress, Brisbane, Australia, 2008. Ashwell, C.M., Angel, R. (2008) Dietary conditioning results in enduring effects on gene expression. Proceedings of the XXIII World Poultry Congress, Brisbane, Australia, 2008.
- Ashwell, C. 2009. Nutritional epigenetics: early life conditioning with dietary phosphorus. Proceedings of the 7th MidAtlantic Nutrition Conference.
- Angel, R. and Ashwell, C. Nutritional Imprinting:Early diet manipulation. Proceedings of the Arkansas Nutrition Conference, 2009.
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Progress 01/01/07 to 12/31/07
Outputs
OUTPUTS: The potential for manipulating the genome by epigenetic modification and selectively regulating gene expression is extremely important in human health. This ability may perhaps provide resistance to disease and metabolic disorders in humans but the potential application in animal agriculture where tight regulation of environmental conditions is possible should be the subject of new research efforts. This project plans to address the issue of epigenetic regulation of gene expression in the chicken. This project is perfectly suited for the NRI Animal Genome: Functional Genomics program element in that it focuses on increasing the understanding of the biological role of the genome (and its regulation) on function, product quality, and efficiency in an agriculturally important animal (chicken) that has significant genome sequence information available. This project will take advantage of the genome sequence to identify regulatory regions that may under go epigenetic regulation of gene expression, an approach that has not been undertaken previously. The project is narrowly focused on the epigenetic regulation of genes in the intestine throughout development and their response to nutritional programming. Successful completion of the project will provide evidence for epigenetic regulation of gene expression in the chicken, demonstrate the mechanism behind "early-life conditioning" previously described in the chicken, and provide a model for future studies to determine the extent of the plasticity of the chicken genome for epigenetic modulation of gene expression by nutritional or other programming stimulus. PARTICIPANTS: Not relevant to this project. TARGET AUDIENCES: Not relevant to this project. PROJECT MODIFICATIONS: Not relevant to this project.
Impacts
Epigenetic regulation of gene expression was initially described as genomic imprinting where a gene is expressed in a parent-of-origin-dependent manner. The primary mechanism for the silencing of a single allele of a gene is by methylation of CpG islands in the regulatory regions of imprinted genes such as insulin-like growth factor 2 and mannose 6-phosphate/insulin-like growth factor 2 receptor. A form of epigenetic regulation has been recently described called fetal "programming". Fueled by epidemiological data the "fetal origins" hypothesis suggests that a poor in utero environment resulting from maternal dietary or placental insufficiency may "program" susceptibility in the fetus to cardiovascular or metabolic disorders. We have observed similar apparent programming by dietary manipulation in the chicken. When birds are challenged with a diet low in phosphorus (P) for 90 hours post-hatch they obtain the ability to better utilize P later in life. This increased retention of P from the diet can partially be explained by an enduring increase in the expression of the intestine-specific sodium phosphorus cotransporter (NaPcoT) gene during programming as well as later in life when fed P restricted diets. The resulting data provide the first evidence for neonatal programming of gene expression in an oviparous species. The reduction of P in the post hatch diet had a significant effect on the expression of the NaPcoT by stimulating an average 2.8-fold increase in the mRNA levels in the small intestine. Nearly identical stimulatory effects were seen across all segments of the intestine with relative expression decreasing from duodenum to ileum. This data correlates well with the apparent increase in efficiency of nutrient uptake measured in these birds. This pattern is similar to that in trout where a 2 fold induction of the NaPcoT was observed as a result of a 40% reduction of diet P. This is also in the range of the induction of expression of the NaPcoT as a result of feeding a low P diet in mice. The effect of reducing P from a control diet level of 0.5% P to a low P diet level of 0.25% P induced NaPcoT expression an average of 2.3 fold. Upon investigation of the genome sequence upstream of the NaPcoT several CpG islands are predicted. Identification of CpG islands is based on relative concentration of CpGs present in a specific sequence. This information along with the other preliminary data demonstrating long term effects on performance and gene expression as a result of nutritional neonatal programming in the chick are evidence for the role of epigenetics in the regulation of these phenomena. Further work must be conducted to elucidate the specifics of neonatal programming in the chicken, the extent of its effects on DNA methylation of the NaPcoT as well as other genes. Demonstrating these epigenetic effects in the chicken will provide both a significant contribution the understanding of the regulation of genomes, particularly in oviparous species but also provide a potential mechanism for improving performance and the economics of poultry production.
Publications
- Druyan, S., Olivera, J.E., Ashwell, C.M. 2008. Focused Microarrays as a Method to Evaluate Subtle Changes in Gene Expression. Poultry Science. 87:2418-2429.
- Yan, F., Angel, R., Ashwell, C.M. 2007. Characterization of the chicken small intestine type IIb sodium phosphate cotransporter. Poultry Science. 86(1):67-77.
- Ashwell, C.M., Angel, R. 2008. Dietary conditioning results in enduring effects on gene expression. Proceedings of the XXIII World Poultry Congress, Brisbane, Australia.
- Angel, R., Ashwell, C.M. 2008. Dietary conditioning results in improved phosphorus utilization. Proceedings of the XXIII World Poultry Congress, Brisbane, Australia.
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