Developmental switch in chromatin structure associated with alternate promoter usage in the Drosophila melanogaster...

During the development of Drosophila melanogaster a switch in alcohol dehydrogenase gene promoter usage occurs, such that proximally initiated mRNA is replaced by mRNA initiated from a more distal location. Investigation of the nucleo-protein organization at this gene in cells inactive for Adh expression, or derived from tissues active at either the proximal or distal promoter, reveals distinct changes in patterns of nucleosome organization and regions of nuclease sensitivity that are strongly correlated with the activity of the gene and its promoter usage. A positioned array of nucleosomes covers the coding region of the inactive gene, but is partially disassembled on gene activation. A series of proximally located hypersensitive sites, detected in early third instar larval fat body cells, are replaced by new, distally located regions of hypersensitivity in late third instar larval fat body, the change apparently coinciding with the promoter switch. Further developmental stage differences are detected in regions over 1 kb upstream of the distal start site. In addition, for both proximally and distally expressing cells, separate and different regions of apparent resistance to DNase I cleavage in chromatin are detected in locations that, in some instances, were previously demonstrated to bind specific factors in vitro.