Showing papers on "X hyperactivation published in 2009"

General gene movement off the X chromosome in the Drosophila genus

Abstract: In Drosophila melanogaster, there is an excess of genes duplicated by retroposition from the X chromosome to the autosomes. Most of those retrogenes that originated on the X chromosome have testis expression pattern. These observations could be explained by natural selection favoring genes that avoided spermatogenesis X inactivation or by sexual antagonistic effects favoring the fixation of male beneficial mutations on the autosomes. If natural selection played the essential role in distributing male-related genes, then the out-of-the-X chromosomal gene movement should not be limited to retrogenes. Here, we studied DNA-based interchromosome gene movement patterns by analyzing relocated genes that were previously identified in 12 Drosophila genome sequences. We found a significant excess of gene movement out of the X chromosome. In addition, we were able to extend previous retrogene movement analysis to species and branches other than those involving D. melanogaster, confirming the pervasiveness of gene movement out of the X chromosome. Also, for X chromosome-to-autosome (X→A) movement, we observed high testis expression of relocated genes as opposed to the low testis expression of parental genes, corroborating the involvement of the male germ line on the gene movement process. These analyses of both DNA-based and RNA-based gene relocations reveal that the out-of-the-X movement of testis-expressed genes is a general pattern in the Drosophila genus.

X chromosome inactivation in clinical practice

Abstract: X chromosome inactivation (XCI) is the transcriptional silencing of the majority of genes on one of the two X chromosomes in mammalian females. Females are, therefore, mosaics for two cell lines, one with the maternal X and one with the paternal X as the active chromosome. The relative proportion of the two cell lines, the X inactivation pattern, may be analyzed by simple assays in DNA from available tissues. This review focuses on medical issues related to XCI in X-linked disorders, and on the value of X inactivation analysis in clinical practice.

A new model for random X chromosome inactivation

Abstract: X chromosome inactivation (XCI) reduces the number of actively transcribed X chromosomes to one per diploid set of autosomes, allowing for dosage equality between the sexes. In eutherians, the inactive X chromosome in XX females is randomly selected. The mechanisms for determining both how many X chromosomes are present and which to inactivate are unknown. To understand these mechanisms, researchers have created X chromosome mutations and transgenes. Here, we introduce a new model of X chromosome inactivation that aims to account for the findings in recent studies, to promote a re-interpretation of existing data and to direct future experiments.

Dosage compensation and gene expression on the mammalian X chromosome: one plus one does not always equal two

Abstract: Counting chromosomes is not just simple math Although normal males and females differ in sex chromosome content (XY vs XX), X chromosome imbalance is tolerated because dosage compensation mechanisms have evolved to ensure functional equivalence In mammals this is accomplished by two processes—X chromosome inactivation that silences most genes on one X chromosome in females, leading to functional X monosomy for most genes in both sexes, and X chromosome upregulation that results in increased gene expression on the single active X in males and females, equalizing dosage relative to autosomes This review focuses on genes on the X chromosome, and how gene content, organization and expression levels can be influenced by these two processes Special attention is given to genes that are not X inactivated, and are not necessarily fully dosage compensated These genes that “escape” X inactivation are of medical importance as they explain phenotypes in individuals with sex chromosome aneuploidies and may impact normal traits and disorders that differ between men and women Moreover, escape genes give insight into how X chromosome inactivation is spread and maintained on the X

The dosage compensation complex shapes the conformation of the X chromosome in Drosophila

Abstract: The dosage compensation complex (DCC) in Drosophila globally increases transcription from the X chromosome in males to compensate for its monosomy. We discovered a male-specific conformation of the X chromosome that depends on the associations of high-affinity binding sites (HAS) of the DCC. The core DCC subunits MSL1-MSL2 are responsible for this male-specific organization. Contrary to emerging concepts, we found that neither DCC assembly nor the conformation of the male X chromosome are influenced by nuclear pore components. We propose that nuclear organization of HAS is central to the faithful distribution of the DCC along the X chromosome.

Clinical and cytological aspects of sex chromosome activity

Abstract: The first known example of a human female with more than one euchromatic X chromosome in somatic cells is presented, viz. a child with 2 normal X chromosomes and the long arm of a third X translocated onto one of the No. 22 chromosomes. In cultured lymphocytes there occurred, in addition to the ordinary Lyon pattern of X chromosome inactivation, 2 other patterns in which (1) 2 normal X chromosomes, and (2) one X and the t(X;22) were euchromatic. As the inactivation within the translocation chromosome did not spread onto chromosome 22, the clinical symptoms of the child had to be attributed to the excess of active X material, not to monosomy 22. Contrary to this, absence of heterochromaty of the Y chromosome does not influence the phenotype, as shown by the case of mixed gonadal dysgenesis with non-fluorescing Y presented. Possible reasons for this difference include: (1) The differences between facultative X and constitutive Y heterochromatin; (2) Different cytologic criteria for heterochromatin may not mean the same kind of inactivity; (3) Differences in phenotypic expression may be due to different chromosomal behaviour among tissues; (4) Late replication and decondensation may not equate genetic inactivity in terms of transcriptional inactivity.

X Chromosome: Expression and Escape

Abstract: Although there are some obvious differences between the X chromosome and the autosomes—such as the X chromosome being present in only one copy in males—the two types of chromosome are remarkably similar in their cytological appearance and gene density [1]. Genomic and transcriptomic studies of Drosophila, however, have revealed two major differences in gene content between the X chromosome and the autosomes. First, there is an excess of functional, duplicate genes that have moved from the X chromosome to the autosomes (Figure 1A) [2]. Second, there is a paucity of genes with male-biased expression on the X chromosome (Figure 1B) [3]. A hypothesis that could explain these observations was proposed by Betran and colleagues in 2002 [2] and is based on the phenomenon of meiotic sex chromosome inactivation (MSCI, see below). Since then, there has been controversy about whether or not MSCI occurs in Drosophila and, if it does, what role it plays in shaping the gene content of the X chromosome. In this issue of PLoS Genetics, Vibranovski et al. [4] present a detailed analysis of gene expression across three stages of Drosophila spermatogenesis. Their results support the occurrence of MSCI and suggest that its effect on germline expression of X-linked genes promotes the selective maintenance of autosomal duplicates arising from X-linked genes. Figure 1 The X chromosome and autosomes of Drosophila melanogaster differ in retrogene and male-biased gene content.