[
Curr Opin Genet Dev,
2016]
In many species, male and female animals differ in the number of X chromosomes they possess. As a consequence, large scale differences in gene dosage exist between sexes; a phenomenon that is rarely tolerated by the organism for changes in autosome dosage. Several strategies have evolved independently to balance X-linked gene dosage between sexes, named dosage compensation (DC). The molecular basis of DC differs among the three best-studied examples: mammals, fruit fly and nematodes. In this short review, we summarize recent microscopic and chromosome conformation capture data that reveal key features of the compensated X chromosome and highlight the events leading to the establishment of a functional, specialized nuclear compartment, the X domain.
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Epigenetics,
2009]
Dosage compensation is an essential process that equalizes X-linked gene dosage between the sexes. In the worm Caenorhabditis elegans, a complex of proteins called the dosage compensation complex (DCC) binds both X chromosomes in hermaphrodites to downregulate gene expression two-fold and hence to reduce X-linked gene expression levels equal to that in males. Five subunits of the DCC form the condensin I(DC) complex, a homolog of the evolutionarily conserved condensin complex required for chromosome segregation and compaction during mitosis and meiosis. How related complexes can perform such diverse functions remains a mystery. Nevertheless, it is believed that the mitotic and interphase functions of condensin are mechanistically related and understanding one process will reveal new insights into the other. We discuss how during worm dosage compensation a condensin-mediated function may guide the organization of the interphase chromatin fibers, leading to the formation of a repressive nuclear compartment.
[
Front Genet,
2014]
In many organisms sexual fate is determined by a chromosome-based method which entails a difference in sex chromosome-linked gene dosage. Consequently, a gene regulatory mechanism called dosage compensation equalizes X-linked gene expression between the sexes. Dosage compensation initiates as cells transition from pluripotency to differentiation. In Caenorhabditis elegans, dosage compensation is achieved by the dosage compensation complex (DCC) binding to both X chromosomes in hermaphrodites to downregulate gene expression by twofold. The DCC contains a subcomplex (condensin I(DC)) similar to the evolutionarily conserved condensin complexes which play a fundamental role in chromosome dynamics during mitosis. Therefore, mechanisms related to mitotic chromosome condensation are hypothesized to mediate dosage compensation. Consistent with this hypothesis, monomethylation of histone H4 lysine 20 is increased, whereas acetylation of histone H4 lysine 16 is decreased, both on mitotic chromosomes and on interphase dosage compensated X chromosomes in worms. These observations suggest that interphase dosage compensated X chromosomes maintain some characteristics associated with condensed mitotic chromosome. This chromosome state is stably propagated from one cell generation to the next. In this review we will speculate on how the biochemical activities of condensin can achieve both mitotic chromosome compaction and gene repression.