Barbara J. Meyer (2005) WormBook "X-Chromosome dosage compensation."

Barbara J. Meyer

[WormBook, 2005]

In mammals, flies, and worms, sex is determined by distinctive regulatory mechanisms that cause males (XO or XY) and females (XX) to differ in their dose of X chromosomes. In each species, an essential X chromosome-wide process called dosage compensation ensures that somatic cells of either sex express equal levels of X-linked gene products. The strategies used to achieve dosage compensation are diverse, but in all cases, specialized complexes are targeted specifically to the X chromosome(s) of only one sex to regulate transcript levels. In C. elegans, this sex-specific targeting of the dosage compensation complex (DCC) is controlled by the same developmental signal that establishes sex, the ratio of X chromosomes to sets of autosomes (X:A signal). Molecular components of this chromosome counting process have been defined. Following a common step of regulation, sex determination and dosage compensation are controlled by distinct genetic pathways. C. elegans dosage compensation is implemented by a protein complex that binds both X chromosomes of hermaphrodites to reduce transcript levels by one-half. The dosage compensation complex resembles the conserved 13S condensin complex required for both mitotic and meiotic chromosome resolution and condensation, implying the recruitment of ancient proteins to the new task of regulating gene expression. Within each C. elegans somatic cell, one of the DCC components also participates in the separate mitotic/meiotic condensin complex. Other DCC components play pivotal roles in regulating the number and distribution of crossovers during meiosis. The strategy by which C. elegans X chromosomes attract the condensin-like DCC is known. Small, well-dispersed X-recognition elements act as entry sites to recruit the dosage compensation complex and to nucleate spreading of the complex to X regions that lack recruitment sites. In this manner, a repressed chromatin state is spread in cis over short or long distances, thus establishing the global, epigenetic regulation of X chromosomes that is maintained throughout the lifetime of hermaphrodites.

Christine E. Schaner et al. (2006) WormBook "Germline chromatin."

Christine E. Schaner, William G. Kelly

[WormBook, 2006]

The DNA in eukaryotes is wrapped around a histone octamer core, together comprising the main subunit of chromatin, the nucleosome. Modifications of the nucleosomal histones in the genome correlate with the ability or inability of chromatin to form higher order structures, that in turn influence gene activity. The genome in primordial germ cells in early C. elegans germ cells carries a unique pattern of histone modifications that correlate with transcriptional repression in these cells, and aspects of this chromatin regulation are conserved in Drosophila. Loss of repression causes sterility in the adults, suggesting that chromatin-based repression is essential for germ line maintenance. The post-embryonic germ line also exhibits unique and dynamic aspects of chromatin regulation, with chromosome-wide regulation particularly evident on the X chromosome. Several properties of X-specific chromatin assembly are also sex-specific. These properties appear to be responding to the meiotic pairing status of the X chromosome, rather than the sex of the germ cells. Finally, gamete-specific chromatin regulation during gametogenesis impacts on X chromatin assembly in the offspring, leading to an apparent sperm-imprinted X inactivation in the early embryo. Other potential roles for germline-specific modes of chromatin assembly in genome regulation and protection are discussed.

Jonathan Hodgkin (2005) WormBook "Karyotype, ploidy, and gene dosage."

Jonathan Hodgkin

[WormBook, 2005]

The normal karyotype of Caenorhabditis elegans, with its five pairs of autosomes and single pair of X chromosomes, is described. General features of chromosomes and global differences between different chromosomal regions are discussed. Abnormal karyotypes, including duplications, deficiencies, inversions, translocations and chromosome fusions are reviewed. The effects of varying ploidy and of varying gene dosage are summarized. Dosage-sensitive genes seem to be rare in C. elegans, and the organism is able to tolerate substantial levels of aneuploidy. However, autosomal hemizygosity for more than about 3 % of the total genome may be incompatible with viability.

John Spieth (2006) WormBook "Overview of gene structure."

John Spieth

[WormBook, 2006]

Throughout the C. elegans sequencing project Genefinder was the primary protein-coding gene prediction program. These initial predictions were manually reviewed by curators as part of a "first-pass annotation" and are actively curated by WormBase staff using a variety of data and information. In the WormBase data release WS133 there are 22,227 protein-coding gene, including 2,575 alternatively-spliced forms. Twenty-eight percent of these have every base of every exon confirmed by transcription evidence while an additional 51% have some bases confirmed. Most of the genes are relatively small covering a genomic region of about 3 kb. The average gene contains 6.4 coding exons accounting for about 26% of the genome. Most exons are small and separated by small introns. The median size of exons is 123 bases, while the most common size for introns is 47 bases. Protein-coding genes are denser on the autosomes than on chromosome X, and denser in the central region of the autosomes than on the arms. There are only 561 annotated pseudogenes but estimates but several estimates put this much higher.

David Zarkower (2006) WormBook "Somatic sex determination."

David Zarkower

[WormBook, 2006]

C. elegans occurs in two natural sexes, the XX hermaphrodite and the XO male, which differ extensively in anatomy, physiology, and behavior. All somatic differences between the sexes result from the differential activity of a global sex determination regulatory pathway. This pathway also controls X chromosome dosage compensation, which is coordinated with sex determination by the action of the three SDC proteins. The SDC proteins control somatic and germline sex by transcriptional repression of the her-1 gene. HER-1 is a secreted protein that controls a regulatory module consisting of a transmembrane receptor, TRA-2 , three intracellular FEM proteins, and the zinc finger transcription factor TRA-1 . The molecular workings of this regulatory module are still being elucidated. Similarity of TRA-2 to patched receptors and of TRA-1 to GLI proteins suggests that parts of the global pathway originally derived from a Hedgehog signaling pathway. TRA-1 controls all aspects of somatic sexual differentiation, presumably by regulating a variety of tissue- and cell-specific downstream targets, including the cell death regulator EGL-1 and the male sexual regulator MAB-3 . Sex determination evolves rapidly, and conservation of sexual regulators between phyla has been elusive. An apparent exception involves DM domain proteins, including MAB-3 , which control sexual differentiation in nematodes, arthropods, and vertebrates. Important issues needing more study include the detailed molecular mechanisms of the global pathway, the identities of additional sexual regulators acting in the global pathway and downstream of TRA-1 , and the evolutionary history of the sex determination pathway. Recently developed genetic and genomic technologies and comparative studies in divergent species have begun to address these issues.