Basic concepts of epigenetics Michal Inbar-Feigenberg, M.D., Sanaa Choufani, Ph.D., Darci T. Butcher, Ph.D., Maian Roifman, M.D., Rosanna Weksberg, M.D., Ph.D.  Fertility and Sterility  Volume 99, Issue 3, Pages 607-615 (March 2013) DOI: 10.1016/j.fertnstert.2013.01.117 Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 1 Epigenetic mechanisms affecting gene expression. Epigenetic patterns are established by a number of mechanisms. Epigenetic marks include DNA methylation and covalent modifications of histone proteins. DNA methylation is established and maintained by the DNMT enzymes. DNA is wrapped around histone protein cores composed of an octamer containing two copies of each core histone: H2A, H2B, H3, and H4. Together, these form the basic unit of chromatin, the nucleosome. Histone modifications are regulated by several enzymes including histone acetyltransferases (HATs) and deacetylases (HDACs). Acetylation of histone proteins by HAT is commonly found in euchromatin (relaxed state of chromatin) and is associated with active transcription. Deacetylation of histone proteins by HDAC and methylation of DNA by DNMTs is a hallmark of heterochromatin (condensed state of chromatin), which is associated with transcriptional repression. Fertility and Sterility 2013 99, 607-615DOI: (10.1016/j.fertnstert.2013.01.117) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions

Figure 2 DNA methylation reprogramming in preimplantation embryos. Soon after fertilization both paternal (blue) and maternal (pink) pronuclei undergo genome-wide demethylation. Although demethylation of the maternal genome lags behind the paternal genome, both are remethylated around the time of implantation (yellow arrow). In contrast to most other genes, epigenetic marks, such as DNA methylation, at imprinted loci (ICs) are established early in germ line development and are protected from the global wave of demethylation early in embryonic development by maintenance DNMT isoforms Dnmt1o, Dnmt1, and several other genes such as NLPR2, NLPR7, and Zfp57. The epigenetic reprogramming of the preimplantation embryo also includes X inactivation. Notably, ART takes place during developmental time periods that involve epigenetic reprogramming. Adapted from reference (109). Fertility and Sterility 2013 99, 607-615DOI: (10.1016/j.fertnstert.2013.01.117) Copyright © 2013 American Society for Reproductive Medicine Terms and Conditions