Dosage compensation

About: Dosage compensation is a research topic. Over the lifetime, 1920 publications have been published within this topic receiving 124589 citations.

The evolutionary causes and consequences of sex-biased gene expression

Abstract: Females and males often differ extensively in their physical traits. This sexual dimorphism is largely caused by differences in gene expression. Recent advances in genomics, such as RNA sequencing (RNA-seq), have revealed the nature and extent of sex-biased gene expression in diverse species. Here we highlight new findings regarding the causes of sex-biased expression, including sexual antagonism and incomplete dosage compensation. We also discuss how sex-biased expression can accelerate the evolution of sex-linked genes.

Aberrant patterns of X chromosome inactivation in bovine clones.

Abstract: In mammals, epigenetic marks on the X chromosomes are involved in dosage compensation. Specifically, they are required for X chromosome inactivation (XCI), the random transcriptional silencing of one of the two X chromosomes in female cells during late blastocyst development. During natural reproduction, both X chromosomes are active in the female zygote. In somatic-cell cloning, however, the cloned embryos receive one active (Xa) and one inactive (Xi) X chromosome from the donor cells. Patterns of XCIhave been reported normal in cloned mice, but have yet to be investigated in other species. We examined allele-specific expression of the X-linked monoamine oxidase type A (MAOA) gene and the expression of nine additional X-linked genes in nine cloned XX calves. We found aberrant expression patterns in nine of ten X-linked genes and hypomethylation of Xist in organs of deceased clones. Analysis of MAOA expression in bovine placentae from natural reproduction revealed imprinted XCI with preferential inactivation of the paternal X chromosome. In contrast, we found random XCI in placentae of the deceased clones but completely skewed XCI in that of live clones. Thus, incomplete nuclear reprogramming may generate abnormal epigenetic marks on the X chromosomes of cloned cattle, affecting both random and imprinted XCI.

Characterization of a prokaryotic SMC protein involved in chromosome partitioning

Abstract: Efficient partitioning of chromosomes into dividing cells is important for cell survival. In Escherichia coli and Bacillus subtilis, chromosomes partition to daughter cells with high fidelity (Hiraga et al. 1989; Ireton et al. 1994). Although proteins, sites, and mechanisms involved in physical separation (decatenation) of bacterial chromosomes have been characterized, much less is known about the mechanisms governing efficient partitioning to daughter cells (for review, see Hiraga 1992; Wake and Errington 1995). Recent work has shown that the chromosomal region around the origin of replication (oriC) is in a defined orientation for most of the bacterial (B. subtilis and E. coli) cell cycle and that newly replicated oriC regions are rapidly separated from each other (Glaser et al. 1997; Gordon et al. 1997; Lin et al. 1997; Webb et al. 1997). The origin regions are found toward the poles of the highly condensed nucleoid body, oriented toward the ends of the cell. The rapid separation and localization of oriC regions indicate the function of a mitotic-like apparatus in prokaryotes (Glaser et al. 1997; Gordon et al. 1997; Lin et al. 1997; Webb et al. 1997). Cellular proteins contributing to efficient chromosome partitioning have recently been characterized. Spo0J from B. subtilis and ParB from Caulobacter crescentus are required for efficient chromosome partitioning and are similar to a family of plasmid-encoded proteins required for plasmid partitioning in E. coli (e.g., ParB for P1 and SopB for F). ParB of C. crescentus is essential for growth, and overexpression causes a defect in chromosome partitioning (Mohl and Gober 1997). Deletion of spo0J in B. subtilis causes an ∼100-fold increase in the number of anucleate cells, resulting in accumulation of 1%–2% anucleate cells in a growing culture (Ireton et al. 1994). Spo0J binds to at least eight sites located in the origin proximal 20% of the chromosome (Lin and Grossman 1998). Spo0J is found in the cell in single discrete foci located near the poles of the nucleoid body (Glaser et al. 1997; Lin et al. 1997), in a pattern similar to that observed for the region around the origin of replication (Lewis and Errington 1997; Webb et al. 1997). Visualization of the foci of Spo0J by immunofluorescence microscopy or by use of a Spo0J–green fluorescent protein (GFP) fusion indicates the assembly of a large nucleoprotein complex containing Spo0J. The function of Spo0J and other proteins of this family is still unknown, though they are thought to be involved in pairing and/or positioning sister chromosomes (Nordstrom and Austin 1989; Niki and Hiraga 1997; Lin and Grossman 1998). The muk genes of E. coli were identified in an elegant screen for mutants that produce anucleate cells (Hiraga et al. 1989). The mukB gene product has features of a myosin-like motor protein and is involved in chromosome condensation and/or movement [(Niki et al. 1991; Hiraga 1992; Wake and Errington 1995; Hu et al. 1996), and references therein]. mukE and mukF, which are in an operon with mukB, are also required for efficient partitioning and their products are thought to interact with MukB (Yamanaka et al. 1996). Of the ∼12 bacterial genomes that have been sequenced, mukB, mukE, and mukF are found only in E. coli and Haemophilus influenzae. B. subtilis, along with many other bacterial species (but not E. coli or H. influenzae), contains a homolog of the eukaryotic Smc (structural maintenance of chromosomes) proteins (Oguro et al. 1996). Several eukaryotes have multiple smc genes, and eukaryotic Smc proteins play a role in chromosome condensation, pairing, and/or segregation (for review, see Hirano et al. 1995; Koshland and Strunnikov 1996; Heck 1997). For example, mutations in the SMC genes of Saccharomyces cerevisiae cause defects in chromosome condensation, segregation, and sister chromatid cohesion (Guacci et al. 1997; Michaelis et al. 1997). DNA condensation by the 13S condensin of Xenopus laevis requires two Smc proteins, XCAP-C and XCAP-E (Hirano et al. 1997). Dosage compensation in Caenorhabditis elegans involves specific interaction of an Smc homolog, Dpy-27, and other proteins, with the X chromosome (Chuang et al. 1994, 1996). Although the precise biochemical function of the Smc proteins is not known, recent work has shown that Smc proteins, or complexes containing Smc proteins, can affect DNA topology in vitro (Kimura and Hirano 1997; Sutani and Yanagida 1997). The smc gene of B. subtilis encodes a 135-kD protein that is homologous to eukaryotic Smc proteins (Oguro et al. 1996). B. subtilis Smc is ∼24% identical and ∼46% similar to SMC1 and SMC2 (S. cerevisiae), XCAP-C and XCAP-E (X. laevis), Dpy-27 (C. elegans), and Cut3 and Cut14 (Schizosaccaromyces pombe). It contains all of the domains associated with the Smc family; an amino-terminal NTP-binding domain, two internal coiled–coil regions separated by a hinge, and the carboxy-terminal signature “DA-box” motif (Hirano et al. 1995; Koshland and Strunnikov 1996). Whereas the existence of Smc proteins in eukaryotes is well documented, their prevalence in bacteria and archaebacteria is only beginning to be appreciated. A search of GenBank and individual sequence databases (both completed and in progress) revealed that at least 11 bacteria and 2 archaebacteria contain genes encoding homologs of Smc. In addition to B. subtilis, the list includes Streptococcus pyogenes, Streptococcus pneumoniae, Mycobacterium tuberculosis, several Mycoplasma species (M. genitalium, M. pneumoniae, and M. hyorhinis), Borrelia burgdorferi, Treponema pallidum, Synechocystis sp., Neisseria gonorrhoeae, and the archaebacteria Methanococcus jannaschii and Archaeoglobus fulgidus. We report the characterization of the B. subtilis smc gene. Null mutations in smc caused a conditional lethal phenotype, alterations in nucleoid appearance, a defect in chromosome partitioning, and a synthetic phenotype with a null mutation in spo0J. These findings indicate that the function of Smc proteins is highly conserved.

Epigenetic modification and inheritance in sexual reversal of fish

Abstract: Environmental sex determination (ESD) occurs in divergent, phylogenetically unrelated taxa, and in some species, co-occurs with genetic sex determination (GSD) mechanisms. Although epigenetic regulation in response to environmental effects has long been proposed to be associated with ESD, a systemic analysis on epigenetic regulation of ESD is still lacking. Using half-smooth tongue sole (Cynoglossus semilaevis) as a model-a marine fish that has both ZW chromosomal GSD and temperature-dependent ESD-we investigated the role of DNA methylation in transition from GSD to ESD. Comparative analysis of the gonadal DNA methylomes of pseudomale, female, and normal male fish revealed that genes in the sex determination pathways are the major targets of substantial methylation modification during sexual reversal. Methylation modification in pseudomales is globally inherited in their ZW offspring, which can naturally develop into pseudomales without temperature incubation. Transcriptome analysis revealed that dosage compensation occurs in a restricted, methylated cytosine enriched Z chromosomal region in pseudomale testes, achieving equal expression level in normal male testes. In contrast, female-specific W chromosomal genes are suppressed in pseudomales by methylation regulation. We conclude that epigenetic regulation plays multiple crucial roles in sexual reversal of tongue sole fish. We also offer the first clues on the mechanisms behind gene dosage balancing in an organism that undergoes sexual reversal. Finally, we suggest a causal link between the bias sex chromosome assortment in the offspring of a pseudomale family and the transgenerational epigenetic inheritance of sexual reversal in tongue sole fish.