Epigenetic regulation during mammalian oogenesis.

The advent of the epigenetic era has sparked a new frontier in molecular research and the understanding of how development can be regulated beyond direct alterations of the genome. Thus far, the focal point of epigenetic regulation during development has been chromatin modifications that control differential gene expression by DNA methylation and histone alterations. But what of events that alter gene expression without direct influence on the DNA itself? The present review focuses on epigenetic pathways regulating development from oogenesis to organogenesis and back that do not involve methylation of cytosine in DNA. We discuss target components of epigenetic modification such as organelle development, compartmentalisation of maternal factors and molecular mediators in the oocyte and how these factors acting during oogenesis impact on later development. Epigenetic regulation of development, be it via cytosine methylation or not, has wide-ranging effects on the subsequent success of a pregnancy and the intrinsic health of offspring. Perturbations in epigenetic regulation have been clearly associated with disease states in adult offspring, including Type II diabetes, hypertension, cancers and infertility. A clear understanding of all epigenetic mechanisms is paramount when considering the increased use of assisted reproductive techniques and the risks associated with their use.

Immunization of nonautoimmune mice with DNA binding domains of the largest subunit of RNA polymerase I results in production of anti-dsDNA and anti-Sm/RNP antibodies.

Antibodies against the N-terminal (NT) but not the basic domain (BD), DNA binding regions of the largest subunit (S1) of RNA polymerase I (RNAPI) were detected in the sera of MRL-lpr/lpr lupus mice. Antibodies against both RNAPI(S1)-NT and -BD, as well as other systemic lupus erythematosus (SLE) autoantigens (La, ribosomal P proteins and Sm/RNP) were produced by rabbits immunized with anti-DNA antibodies that had been affinity purified from SLE patients. Immunization of nonautoimmune mice (Balb/c) with RNAPI(S1)-NT, RNAPI(S1)-BD, or La in the form of GST fusion proteins, induced production of anti-double-stranded (ds) DNA and anti-Sm/RNP. GST-P1 did not induce an anti-dsDNA response in these mice. These results demonstrate that RNAPI(S1)-NT, RNAPI(S1)-BD and La can participate in an anti-autoantigen/anti-DNA antibody loop during an SLE-like autoimmune response.