Painting of fourth and chromosome-wide regulation of the 4th chromosome in Drosophila melanogaster

Abstract

Drosophila melanogaster exhibits two expression-regulating systems that target whole, specific chromosomes: the dosage compensation system whereby the male-specific lethal complex doubles transcription of genes on the male X-chromosome and the chromosome 4-specific protein Painting of fourth, POF. POF is the first example of an autosome-specific protein and its presence raises the question of the universality of chromosome-specific regulation. Here we show that POF and heterochromatin protein 1 (HP1) are involved in the global regulation of the 4th chromosome. Contrary to previous conclusions, Pof is not essential for survival of diplo-4th karyotype flies. However, Pof is essential for survival of haplo-4th individuals and expression of chromosome 4 genes in diplo-4th individuals is decreased in the absence of Pof. Mapping of POF using chromatin immunoprecipitation suggested that it binds within genes. Furthermore, we show that POF binding is dependent on heterochromatin and that POF and HP1 bind interdependently to the 4th chromosome. We propose a balancing mechanism involving POF and HP1 that provides a feedback system for fine-tuning expression status of genes on the 4th chromosome.

Elevated levels of expression associated with regions of theDrosophilagenome that lack crossing over

“…Interestingly, it has been reported that the protein 'Painting of fourth' (POF) exclusively binds to the fourth chromosome in Drosophila (Larsson et al 2004). The extent of POF binding to fourth chromosome genes is correlated with their transcription levels, and mutational knockouts of POF lead to reduced gene expression on the fourth chromosome (Johansson et al 2007). This suggests that it is involved in chromosome 4-specific gene regulation, perhaps even having a dosage compensation-like role.…”

Coordinated Regulation of Heterochromatic Genes inDrosophila melanogasterMales

“…In the related D. ananassae and D. malerkotliana, POF binds to the fourth chromosome of both sexes but colocalizes with MSL3 on the male X chromosome, suggesting a role in X chromosome compensation in these species (Larsson et al 2004). While POF is nonessential in D. melanogaster with two fourth chromosomes, it is necessary for the survival of flies with a single fourth chromosome, suggesting that POF functions in dosage compensation of the D. melanogaster fourth chromosome ( Johansson et al 2007). POF is a putative RNA-binding protein.…”

“…A deleted cosmid lacking w 1 was used in studies of PEV [w À 4D4.3]. Mutations in msl1, msl2, msl3, and pof have been previously described (Lindsley and Zimm 1992;Johansson et al 2007). Variegating transgene insertions used in this study have been described (Sun et al 2000;Maggert and Golic 2002;Yanet al 2002).…”

POF Regulates the Expression of Genes on the Fourth Chromosome in Drosophila melanogaster by Binding to Nascent RNA

“…The evolution of dosage compensation mechanisms is attributable to evolutionary pressures that act at all levels of expression to compensate for the losses of functional gene copies. Two dosage compensation systems have been studied in Drosophila: the male-specific lethal (MSL) complex, which targets and upregulates the male X chromosome (18,23,56), and the painting of fourth (POF) protein, which stimulates the expression of the fourth chromosome in Drosophila melanogaster but is believed to have originated from a dosage-compensating mechanism (26,(33)(34)(35). The MSL complex and POF coexist; they are on different chromosomes in, e.g., D. melanogaster, but are colocalized on the same chromosome in, e.g., Drosophila ananassae.…”