Balancing up and downregulation of the C. elegans X chromosomes

Abstract

In Caenorhabditis elegans, males have one X chromosome and hermaphrodites have two. Emerging evidence indicates that the male X is transcriptionally more active than autosomes to balance the single X to two sets of autosomes. Because upregulation is not limited to males, hermaphrodites need to strike back and downregulate expression from the two X chromosomes to balance gene expression in their genome. Hermaphrodite-specific downregulation involves binding of the dosage compensation complex to both Xs. Advances in recent years revealed that the action of the dosage compensation complex results in compaction of the X chromosomes, changes in the distribution of histone modifications, and ultimately limiting RNA Polymerase II loading to achieve chromosome-wide gene repression.

Figure 1. Regulation of the X chromosomes in Caenorhabditis elegans

Although the mechanism of upregulation is not known, it is believed that the X chromosomes in C. elegans are transcriptionally more active than the autosomes (green X chromosomes). X-upregulation balances the single X to two sets of autosomes in males, but creates X overexpression in hermaphrodites. A second, and better understood, mechanism then downregulates both X chromosomes by half, to restore genomic balance in hermaphrodites (red X chromosomes).

Figure 2. The dosage compensation complex (DCC)

The DCC consists of a five subunit condensin complex, as well as at least five additional subunits. Several of its subunits are also members of other complexes and perform DCC-independent functions as well. Condensin I^DC shares four of its five subunits with condensin I, and one subunit with condensin II. Several DCC subunits need to be sumoylated. In case of dual function subunits, such as DPY-28, the protein is only sumoylated when part of the DCC. DPY-30, in addition to interacting with several DCC members, is also part of the COMPASS/MLL histone methyltransferase complex. DPY-21 has both DCC-dependent and DCC-independent functions, although the context of its DCC-independent function is not known.

Figure 3. Summary of DCC-mediated changes in chromatin and chromosome compaction

As a result of DCC function, the X chromosomes (shown in red) in hermaphrodites compact to take up a smaller portion of the nucleus than what would be predicted by DNA content. Compaction is accompanied by enrichment of H4K20me1 (gray flags) and depletion of H4K16ac (green flags). These changes are consistent with a mechanism related to mitotic chromosome condensation.