Identification of a putative promoter element in intron5 of the RUNX1 gene (565.2)

t(8:21) is one of the most frequent chromosomal translocation found in acute myeloid leukemia (AML) and involves RUNX1 and ETO genes. To date all the break points mapped are located in intron 5 of RUNX1 gene. Interestingly, this intron exhibits DNaseI hypersensitive sites, which has been associated to cis regulatory elements. Therefore, we hypothesize that regulatory elements are harbored in intron5 of the RUNX1 gene. In order to test this hypothesis, we performed bioinformatics analysis of ChIPseq data available from the server ENCODE to identify regions of intron 5 enriched in epigenetics marks associated with regulatory elements. We show that in hematopoietic cells one region is enrich in K4H3me, K4H3me3 and K27H3ac that co-localizes with DNaseI hypersensitive sites. These marks have been associated with promoter modules. Indeed, when we cloned this region (PPR=putative promoter region) in a reporter vector, we found that it activates expression of the reporter gene in an orientation dependent manner. ...