Gene Silencing Linked to Fetal Growth and Diabetes

May 9, 2008

In a rat model of intrauterine growth retardation, which has been linked to diabetes in adulthood, a gene important for pancreatic β-cell function and development undergoes epigenetic changes that result in its silencing after diabetes onset, according to research published online May 8 in the Journal of Clinical Investigation.

FRIDAY, May 9 (HealthDay News) -- In a rat model of intrauterine growth retardation, which has been linked to diabetes in adulthood, a gene important for pancreatic β-cell function and development undergoes epigenetic changes that result in its silencing after diabetes onset, according to research published online May 8 in the Journal of Clinical Investigation.

Jun H. Park, from Children's Hospital of Philadelphia, and colleagues examined the role of the Pdx1 gene, a transcription factor important for pancreatic β-cell function and development, and epigenetic modification in a rat model of intrauterine growth retardation.

The researchers found that the rats had permanently reduced expression of Pdx1 in β-cells. The gene underwent epigenetic modifications throughout fetal development, following birth, during the neonatal period and in adulthood involving various changes in protein binding and changes in methylation and acetylation state. The Pdx1 locus was permanently silenced after the development of diabetes in adulthood.

"These results provide insight into the development of type 2 diabetes following intrauterine growth retardation and we believe they are the first to describe the ontogeny of chromatin remodeling in vivo from the fetus to the onset of disease in adulthood," Park and colleagues conclude.

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