Genetic and molecular analysis of wings apart-like (wapl), a gene controlling heterochromatin organization in Drosophila melanogaster

Mutations in the X-linked gene wings apart-like (wapl) result in late larva l lethality associated with an unusual chromosome morphology. In brain cell metaphases of wapl mutants, sister chromatids of all chromosomes are align ed parallel to each other instead of assuming the typical morphology observ ed in wild type. This effect is due to a loosening of the adhesion between sister chromatids in the heterochromatic regions of the chromosomes. Despit e this aberrant chromosome morphology, mutant brains exhibit normal mitotic parameters, suggesting that heterochromatin cohesion is not essential for proper centromere function. On the basis of these observations, we examined the role of wapl in meiotic chromosome segregation in females. wapl exhibi ts a dear dominant effect on achiasmate segregation, giving further support to the hypothesis that proximal heterochromatin is involved in chromosome pairing during female meiosis. We also examined whether wapl modulates posi tion-effect variegation (PEV). Our analyses showed that wapl is a dominant suppressor of both white and Stubble variegation, while it is a weak enhanc er of brown variegation. wapl maps to region 2D of the X chromosome between Pgd and pn. Mie identified the wapl gene within a pretiously conducted chr omosomal walk in this region. The wapl transcriptional unit gives rise to t wo alternatively spliced transcripts 6.5- and 5-kb long. The protein encode d by the larger of these transcripts appears to be conserved among higher e ukaryotes and contains a tract of acidic amino acids reminiscent of many ch romatin-associated proteins, including two [HPl and SU(VAR) 3-7] encoded by other genes that act as suppressors of PEV.