Chromatin immunoselection defines a TAL-1 target gene

Despite the major functions of the basic helix–loop–helix transcription factor TAL‐1 in hematopoiesis and T‐cell leukemogenesis, no TAL‐1 target gene has been identified. Using immunoprecipitation of genomic fragments bound to TAL‐1 in the chromatin of murine erythro‐leukemia (MEL) cells, we found that 10% of the immunoselected fragments contained a CAGATG or a CAGGTG E‐box, followed by a GATA site. We studied one of these fragments containing two E‐boxes, CAGATG and CAGGTC, followed by a GATA motif, and showed that TAL‐1 binds to the CAGGTG E‐box with an affinity modulated by the CAGATG or the GATA site, and that the CAGGTG–GATA motif exhibits positive transcriptional activity in MEL but not in HeLa cells. This immunoselected sequence is located within an intron of a new gene co‐expressed with TAL‐1 in endothelial and erythroid cells, but not expressed in fibroblasts or adult liver where no TAL‐1 mRNA was detected. Finally, in vitro differentiation of embryonic stem cells towards the erythro/megakaryocytic pathways showed that the TAL‐1 target gene expression followed TAL‐1 and GATA‐1 expression. These results establish that TAL‐1 is likely to activate its target genes through a complex that binds an E‐box–GATA motif and define the first gene regulated by TAL‐1.