Dosage compensation in C. elegans is implemented by five autosomal genes,
dpy-21,
dpy-26,
dpy-27,
dpy-28 and
dpy-30, whose activity states are set in response to the primary sex-determination signal, the X/A ratio. This ratio coordinately controls sex determination and dosage compensation by regulating the male specific gene
xol-1. A low level of
xol-1 activity in XX animals leads to activation of the hermaphrodite specific genes
sdc-1,
sdc-2 and
sdc-3 and implementation of dosage compensation. Recent molecular epistasis experiments have shown that DPY-26 and DPY-27 localize to the X chromosomes of XX animals in a manner dependent on the X chromosome localization of SDC-2 and SDC-3 (See abstracts by H . E. Dawes, T. Davis, J. D. Lieb and M. R. Albrecht). It is likely that the dosage compensation complex thus formed alters the higher order structure of the X chromosomes in XX animals so as to lower the level of X-linked transcript levels (Chuang et al. 1995).
dpy-21 is unique among the genes required strictly for dosage compensation in that it is not provided maternally, and the wild-type product is not essential for viability.
dpy-21 also differs from other dosage compensation genes in that
dpy-21 XO animals have altered levels of X-linked gene expression, although they are phenotypically wild-type.
dpy-21 is not required for assembly of the dosage compensation complex; similarly,
sdc-1 appears to play no role in the complex assembly. I found that the original mapping data for this gene was incorrect and subsequently correctly localised it to a 1 Mb region using a PCR based assay for sequence-tagged sites. The gene was then localised to a still smaller region by mapping the breakpoints of a
dpy-21 deficiency. RFLP analysis narrowed the
dpy-21 locus to two YACs that represent a region of the genome unclonable in standard E. coli vectors. I generated YAC sublibraries from which a polymorphic phage clone was isolated. Further RFLP analysis suggests that
dpy-21 is closely linked to this clone. I am currently generating a sublibrary in fosmids (F factor-based replicon) in order to overcome the difficulties of cloning the region in phage and cosmid vectors.