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Early-Life Stress Induced Epigenetic Changes of Corticotropin-Releasing Factor Gene in Anorexic Low Body Weight–Selected Chicks

1
Department of Animal and Poultry Sciences, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
2
School of Neuroscience, Virginia Polytechnic Institute and State University, Blacksburg, VA 24061, USA
*
Author to whom correspondence should be addressed.
Life 2020, 10(5), 51; https://doi.org/10.3390/life10050051
Received: 18 March 2020 / Revised: 16 April 2020 / Accepted: 22 April 2020 / Published: 27 April 2020
(This article belongs to the Section Animal Science)
The expression of neuropeptide Y (NPY) in the arcuate nucleus (ARC) and corticotropin-releasing factor (CRF) in the paraventricular nucleus (PVN) were increased when low body weight–selected (LWS) line chicks, which are predisposed to anorexia, were subjected to a combination of nutritional and thermal stressors at hatch. We hypothesized that such changes resulted from epigenetic modifications. We determined global DNA methylation, DNA methyltransferase (DNMT) activity, and methylation near the promoter regions of NPY and CRF, in the hypothalamus of LWS chicks on day 5 post-hatch. Stress exposure at hatch induced global hypermethylation and increased DNMT activity in the ARC but not PVN. In the PVN of stressed LWS chicks, there was decreased methylation of a CpG site located at the core binding domain of methyl cytosine binding domain protein 2 (MBD2), near the CRF gene promoter. We then demonstrated that this was associated with disrupted binding of MBD2. There was also reduced utilization of yolk reserves and lean and fat masses in chicks that were stress-exposed. These findings provide novel insights on molecular mechanisms through which stressful events induce or intensify anorexia in predisposed individuals and a novel molecular target for further studies. View Full-Text
Keywords: anorexia; ARC; chicks; CRF; DNA methylation; early-life stressor; hypothalamus; MBD2; NPY; PVN anorexia; ARC; chicks; CRF; DNA methylation; early-life stressor; hypothalamus; MBD2; NPY; PVN
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MDPI and ACS Style

Xiao, Y.; Wang, J.; Siegel, P.B.; Cline, M.A.; Gilbert, E.R. Early-Life Stress Induced Epigenetic Changes of Corticotropin-Releasing Factor Gene in Anorexic Low Body Weight–Selected Chicks. Life 2020, 10, 51.

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