Seminars

CpG islands (CGIs) function as promoters for approximately 60% of human genes. Most of these elements remain protected from CpG methylation, an otherwise prevalent epigenetic modification that is associated with transcriptional silencing. Here I will first describe our observations that suggest that protection from DNA methylation is a built-in characteristic of the DNA sequence of CGI promoters that is revealed by the co-transcriptional formation of R-loop structures. I will then describe novel genomics methodologies that enable us to measure global RNA:DNA hybrid formation and describe our early observations in the human genome and their implications for transcriptional control and genome stability. Finally, I will introduce new observations that link excessive formation of RNA:DNA hybrids to specific auto-immune conditions in humans.