[
Curr Opin Genet Dev,
1998]
Dosage compensation ensures that individuals with a single X chromosome have the same amount of most X-linked gene products as those with two. In Drosophila, this equalization is achieved by a two-fold enhancement of the level of transcription of the X in males (XY) relative to each X chromosome in females (XX). In Caenorhabditis, equalization of X-linked gene products between hermaphrodites (XX) and males (XO) is achieved by decreasing the activity of genes in the former. These two different solutions to the common problem of unequal dosage of X-linked genes in different sexes provide invaluable paradigms for the study of gene regulation at the level of chromatin remodeling.
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Int Rev Cell Mol Biol,
2010]
In many animals and some fungi, mechanisms have been described that target unpaired chromosomes and chromosomal regions for silencing during meiotic prophase. These phenomena, collectively called "meiotic silencing," target sex chromosomes in the heterogametic sex, for example, the X chromosome in male nematodes and the XY-body in male mice, and also target any other chromosomes that fail to synapse due to mutation or chromosomal rearrangement. Meiotic silencing phenomena are hypothesized to maintain genome integrity and perhaps function in setting up epigenetic control of embryogenesis. This review focuses on meiotic silencing in the nematode, Caenorhabditis elegans, including its mechanism and function(s), and its relationship to other gene silencing processes in the germ line. One hallmark of meiotic silencing in C. elegans is that unpaired/unsynapsed chromosomes and chromosomal regions become enriched for a repressive histone modification, dimethylation of histone H3 on lysine 9 (H3K9me2). Accumulation and proper targeting of H3K9me2 rely on activity of an siRNA pathway, suggesting that histone methyltransferase activity may be targeted/regulated by a small RNA-based transcriptional silencing mechanism.
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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.