Cover photograph (Copyright © 2008, American Society for Microbiology. All Rights Reserved.): R-loops are known to form at mammalian immunoglobulin class switch sequences, and upon transcription through the region, the RNA transcript hybridizes with the template DNA strand. The leading edge of an R-loop is depicted in the foreground with the RNA strand (red or orange) coming out of the RNA polymerase (the gear wheels) and getting hybridized with the template DNA strand (green), whereas the nontemplate DNA strand (blue) is forced to exist in single-stranded form. The direction of transcription is from top to bottom, and the double-stranded DNA is seen on the extreme bottom edge. In the background (not necessarily representing a data set from the article), each set of vertical lines depicts an R-looped molecule with each horizontal line representing a C to T change similar to the R-loop representations derived from sodium bisulfite treatment of transcribed switch substrates. The cover was designed by Deepankar Roy with help from Albert Tsai. (See related article on p. 50.)