Transcriptional regulation and spatial organisation of the human AML1/RUNX1 gene

The transcription factor RUNX1 is a key regulator of haematopoiesis in vertebrates. In humans, the 260-kb long gene coding for this transcription factor is located on chromosome 21. This gene is transcribed from two alternative promoters that are commonly referred to as the distal and the proximal promoters. In model experiments, these two promoters were found to be active in cells of different lineages, although RUNX1 is preferentially expressed in haematopoietic cells. In the present study, we attempted to identify the regulatory elements that could guide tissue-specific expression of the RUNX1 gene. Two such regulatory elements were found within the RUNX1 gene. One of these elements, located within intron 1, is a haematopoietic-specific enhancer. The second regulatory element, located within intron 5.2, contributes to the formation of an active chromatin hub, which integrates the above-mentioned enhancer and the P1 and P2 promoters.