Vernì F, Gandhi R, Goldberg M L, Gatti M
Istituto Pasteur-Fondazione Cenci Bolognetti, Dipartimento di Genetica e Biologia Molecolare, Universitá di Roma La Sapienza, 00185 Rome, Italy.
Genetics. 2000 Apr;154(4):1693-710. doi: 10.1093/genetics/154.4.1693.
Mutations in the X-linked gene wings apart-like (wapl) result in late larval lethality associated with an unusual chromosome morphology. In brain cell metaphases of wapl mutants, sister chromatids of all chromosomes are aligned parallel to each other instead of assuming the typical morphology observed in wild type. This effect is due to a loosening of the adhesion between sister chromatids in the heterochromatic regions of the chromosomes. Despite 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 exhibits a clear 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 position-effect variegation (PEV). Our analyses showed that wapl is a dominant suppressor of both white and Stubble variegation, while it is a weak enhancer of brown variegation. wapl maps to region 2D of the X chromosome between Pgd and pn. We identified the wapl gene within a previously conducted chromosomal walk in this region. The wapl transcriptional unit gives rise to two alternatively spliced transcripts 6.5- and 5-kb long. The protein encoded by the larger of these transcripts appears to be conserved among higher eukaryotes and contains a tract of acidic amino acids reminiscent of many chromatin-associated proteins, including two [HP1 and SU(VAR)3-7] encoded by other genes that act as suppressors of PEV.
X连锁基因“翅分离样”（wapl）的突变导致幼虫后期致死，并伴有异常的染色体形态。在wapl突变体的脑细胞中期，所有染色体的姐妹染色单体彼此平行排列，而不是呈现野生型中观察到的典型形态。这种效应是由于染色体异染色质区域中姐妹染色单体之间的黏附力减弱所致。尽管染色体形态异常，但突变体大脑表现出正常的有丝分裂参数，这表明异染色质凝聚对于着丝粒的正常功能并非必不可少。基于这些观察结果，我们研究了wapl在雌性减数分裂染色体分离中的作用。wapl对无交叉分离表现出明显的显性效应，进一步支持了近端异染色质参与雌性减数分裂期间染色体配对的假说。我们还研究了wapl是否调节位置效应斑驳（PEV）。我们的分析表明，wapl是白色和刚毛斑驳的显性抑制因子，而它是棕色斑驳的弱增强因子。wapl定位于X染色体2D区域，在Pgd和pn之间。我们在该区域先前进行的染色体步移中鉴定出了wapl基因。wapl转录单元产生两种长度分别为6.5 kb和5 kb的可变剪接转录本。这些转录本中较大的那个所编码的蛋白质在高等真核生物中似乎是保守的，并且包含一段酸性氨基酸序列，让人联想到许多与染色质相关的蛋白质，包括由其他作为PEV抑制因子的基因所编码的两种蛋白质[HP1和SU(VAR)3-7]。
