Southern blot analysis in the promoter region of

mdr1a. Genomic DNA of each P388 derivative was digested with MspI (A) or HpaII (B) and analyzed by Southern blotting using the PstI-digested 370-bp fragment as a probe (░, C). The physical maps of the mdr1a5′-flanking region without rearrangement (upper) and with putative rearrangement (lower) are presented in panel C. The open box and horizontal arrow correspond to mdr1a exon-1 and its transcriptional direction, respectively. Vertical arrows indicateMspI/HpaII sites. In the lower map the broken line represents the putative rearranged DNA, and the expectedMspI/HpaII site is indicated as site a′. The restriction patterns of HpaII suggested that site a was hypermethylated, and both sites b and c were hypomethylated.