broad epigenetic signature of maternal care in the brain of adult rats广泛的表观遗传签名母性关怀的成年老鼠的大脑.pdf

Broad Epigenetic Signature of Maternal Care in the Brain of Adult Rats 1,2,3 . 2,4,5. 1,2,3. 4 Patrick O. McGowan * , Matthew Suderman , Aya Sasaki , Tony C. T. Huang , Michael Hallett5, Michael J. Meaney1,2,6,7, Moshe Szyf2,4,7* 1 Douglas Mental Health University Institute, Montreal, Quebec, Canada, 2 Sackler Program for Epigenetics and Developmental Psychobiology at McGill University, McGill University, Montreal, Quebec, Canada, 3 Centre for the Neurobiology of Stress, University of Toronto, Scarborough, Toronto, Ontario, Canada, 4 Department of Pharmacology and Therapeutics, McGill University, Montreal, Quebec, Canada, 5 McGill Centre for Bioinformatics, McGill University, Montreal, Quebec, Canada, 6 Singapore Institute for Clinical Sciences, Singapore, Republic of Singapore, 7 Experience-Based Brain and Biological Development Program of the Canadian Institute for Advanced Research, Toronto, Ontario, Canada Abstract Background: Maternal care is associated with long-term effects on behavior and epigenetic programming of the NR3C1 (GLUCOCORTICOID RECEPTOR) gene in the hippocampus of both rats and humans. In the rat, these effects are reversed by cross-fostering, demonstrating that they are defined by epigenetic rather than genetic processes. However, epigenetic changes at a single gene promoter are unlikely to account for the range of outcomes and the persistent change in expression of hundreds of additional genes in adult rats in response to differences in maternal care. Methodology/Principal Findings: We examine here using high-density oligonucleotide array the state of DNA methylation, histone acetylation and gene expression in a 7 million base pair region of chromosome 18 containing