Chromosomal Binding Sites of the Homeotic Cofactor Homothorax

The Meis family oncoproteins play a crucial role in leukemogenesis and are highly expressed in other types of cancer as well. The transforming potential of Meis proteins depends on their ability to activate gene expression and therefore, revealing the identity of their target genes is very important. The genome of the fruit fly Drosophila melanogaster contains a single Meis gene, homothorax (hth), which plays multiple roles in embryonic and adult development. Mutations in hth affect the development of numerous embryonic and adult tissues, suggesting that Hth regulates the transcription of a large number of genes. However, it is not known how many genes are regulated directly by Hth and what is the nature of these genes. To address this question, we examined the distribution of the in vivo binding sites of Hth on polytene chromosomes. We found that in the salivary glands (SG) of third instar larvae, Hth binds to approximately 150 chromosomal sites in a very reproducible pattern. More than hundred of these sites were mapped cytologically. Interestingly, Hth accumulates at high levels in some of the most prominent hormone-induced chromosomal puffs, pointing to a possible role of Hth in activation of ecdysone-induced targets. Interfering with the normal transcriptional activity of Hth in larval SGs leads to dramatic reduction in cell size and DNA content implicating Hth in the regulation of cell growth and endoreplication in larval SGs.