A genetic screen for regulators of Drosophila histone H1 binding and chromosome structure in vivo

Histone H1 and related linker histones play critical roles in chromosome organization in eukaryotic cells. Although histone H1 is essential for compacting nucleosomes into chromatin fibers and is a major structural component of chromosomes, its association with chromatin is highly dynamic. Histone H1 exchange modulates the accessibility of regulatory proteins to DNA and has been implicated in the regulation of gene expression and cellular pluripotency. Relatively little is known, however, about how histone H1 binding, exchange, and function are regulated in vivo. In this study, we investigated the regulation of histone H1 function in Drosophila using live analysis and confocal microscopy. A gain-of-function genetic screen identified several factors that affect chromosome structure, histone H1 binding, or histone H1 exchange, including the ATP-dependent chromatin-remodeling factor XNP, the hypoxia-induced factor Scylla, the winged helix transcription factor Jumeau, and the microRNA bantam. Our findings show that altered expression of single factors can have surprisingly global effects on higher-order chromatin structure and histone H1 binding in vivo, with the potential to trigger large-scale changes in genome organization and accessibility.