Abstract

t(8:21) is one of the most frequent chromosomal translocation found in leukemia. To date all the break points mapped for this translocation are clustered in three specifics regions (calledBCRs = break clusters regions) located inside intron 5 of theRUNX1 gene. Interestingly, two of the BCRs exhibit DNase I hypersensitive sites, which have been widely associated with cis regulatory elements. Therefore, we hypothesize that regulatory elements are harbored in the BCRs in intron 5 of the RUNX1gene. In order to test this hypothesis, we performed Chromatin Inmunoprecipitation assays to identify regions in intron 5 of theRUNX1 gene enriched in epigenetics marks characteristic of regu-atory elements. Interestingly, our results shown one region enriched in H3 and H4 acetylated and in H3K27ac. These marks have been associated with promoter modules. Indeed, when wecloned this region (PRR = Putative Regulatory Region) in the pGL3 basic reporter vector, we found that it activates expression of the luciferase reporter gene in an orientation dependent manner. Moreover, when we analyze putative transcription factorsbinding sites, we found one RUNX binding motif. Indeed whenwe transfected the promoter with RUNX1 expression vector wefound that RUNX1 modulates the expression of PRR.