Dr. Corces is a professor of Human Genetics at the Emory University School of Medicine. Research in Dr. Corces' laboratory studies the mechanisms by which the three-dimensional organization of the chromatin is established and maintained. His current research focuses on understanding the mechanisms by which the environment alters the epigenome of germline cells and how these epigenetic alterations can be transmitted from the gametes to the embryo after fertilization to cause disease states that can be passed on to subsequent generations. He has published extensively in the area of epigenetics and genomics, with a recent focus on the 3D organization of the nucleus of egg and sperm and the mechanisms of transgenerational inheritance of epiphenotypes. 

CTCF regulates the transgenerational transmission of epiphenotypes in mice 

The mechanisms by which epiphenotypes are transmitted tran-sgenerationally through the parental germlines in mammals are poorly understood. Exposure of pregnant mouse F0 females during E7.5-E13.5 to bisphenol A results in obesity in the F2 progeny in the absence of additional exposure. This epiphenotype can be transmitted through the male and female germlines up to the F5 generation, decreases in F6, and disappears in F7. Analyses of chromatin changes in the sperm of the F1 generation reveal a widespread increase in chromatin accessibility at binding sites for CTCF and other transcription factors accompanied by alterations in 3D organization. Comparison of the transmission of obesity between F2 and F5 and its disappearance in F7 with alterations in the binding of these transcription factors points to the recruitment of CTCF to a new site located in an intron of the Fto gene and activation of two different enhancers. Deletion of the CTCF site using CRISPR-Cas9 results in mice that fail to gain weight after ancestral BPA exposure. Based on observations from Hi-C data, we suggest that the two enhancers form an autoregulatory feedback loop that, in combination with a decrease of m6A in sperm enhancer RNAs, may cause alterations of gene expression in the embryo after fertilization. Given the established involvement of SNPs in FTO in human obesity, the results suggest that both genetic and epigenetic alterations of the same gene can lead to the same phenotypic outcomes on human health.