FIGURE 5.
Schematic representation of the BLV 5′-LTR aligned with the CpG methylation pattern of the L267 cell line. The transcription initiation site at the U3–R junction of the 5′-LTR (mRNA start site is at +1 nt) is indicated by an arrow. The TxREs are three major transcriptional enhancer sequences of 21 bp, which interact with the cellular transcription factors CREB, CREM, ATF-1, and ATF-2 and which are required for the transcriptional activation of the BLV LTR by the virus-encoded TaxBLV transactivator. Each of the 21-bp enhancers contains a sequence homologous to the consensus E-box binding motif (E-box1, E-box2, and E-box3) overlapping an imperfect CRE (CRE1, CRE2, and CRE3). The U3 region also contains a glucocorticoid-responsive element (GRE) and a PU.1/Spi-B site. A USF-1/USF-2 binding site (E-box 4) and an interferon regulatory factor (IRF-1/IRF-2)-binding site are located in the R region and the U5 region, respectively. The results of bisulfite genomic sequencing that we obtained in the L267 cell line are aligned with the schematic representation of the 5′-LTR. The complete nucleotide sequence of the U3 region is shown with the transcription factor binding sites indicated by arrows and all of the CpG dinucleotides shown in boxes. me, methylated CpGs. DAS, downstream activating sequence.