Showing papers on "X hyperactivation published in 2006"

Dosage compensation of the active X chromosome in mammals.

Abstract: Monosomy of the X chromosome owing to divergence between the sex chromosomes leads to dosage compensation mechanisms to restore balanced expression between the X and the autosomes In Drosophila melanogaster, upregulation of the male X leads to dosage compensation It has been hypothesized that mammals likewise upregulate their active X chromosome Together with X inactivation, this mechanism would maintain balanced expression between the X chromosome and autosomes and between the sexes Here, we show that doubling of the global expression level of the X chromosome leads to dosage compensation in somatic tissues from several mammalian species X-linked genes are highly expressed in brain tissues, consistent with a role in cognitive functions Furthermore, the X chromosome is expressed but not upregulated in spermatids and secondary oocytes, preserving balanced expression of the genome in these haploid cells Upon fertilization, upregulation of the active X must occur to achieve the observed dosage compensation in early embryos

Global analysis of X-chromosome dosage compensation

Abstract: Drosophila melanogaster females have two X chromosomes and two autosome sets (XX;AA), while males have a single X chromosome and two autosome sets (X;AA). Drosophila male somatic cells compensate for a single copy of the X chromosome by deploying male-specific-lethal (MSL) complexes that increase transcription from the X chromosome. Male germ cells lack MSL complexes, indicating that either germline X-chromosome dosage compensation is MSL-independent, or that germ cells do not carry out dosage compensation. To investigate whether dosage compensation occurs in germ cells, we directly assayed X-chromosome transcripts using DNA microarrays and show equivalent expression in XX;AA and X;AA germline tissues. In X;AA germ cells, expression from the single X chromosome is about twice that of a single autosome. This mechanism ensures balanced X-chromosome expression between the sexes and, more importantly, it ensures balanced expression between the single X chromosome and the autosome set. Oddly, the inactivation of an X chromosome in mammalian females reduces the effective X-chromosome dose and means that females face the same X-chromosome transcript deficiency as males. Contrary to most current dosage-compensation models, we also show increased X-chromosome expression in X;AA and XX;AA somatic cells of Caenorhabditis elegans and mice. Drosophila germ cells compensate for X-chromosome dose. This occurs by equilibrating X-chromosome and autosome expression in X;AA cells. Increased expression of the X chromosome in X;AA individuals appears to be phylogenetically conserved.

A locus for familial skewed X chromosome inactivation maps to chromosome Xq25 in a family with a female manifesting Lowe syndrome.

Abstract: In mammals, X-linked gene products can be dosage compensated between males and females by inactivation of one of the two X chromosomes in the developing female embryos. X inactivation choice is usually random in embryo mammals, but several mechanisms can influence the choice determining skewed X inactivation. As a consequence, females heterozygous for X-linked recessive disease can manifest the full phenotype. Herein, we report a family with extremely skewed X inactivation that produced the full phenotype of Lowe syndrome, a recessive X-linked disease, in a female. The X chromosome inactivation studies detected an extremely skewed inactivation pattern with a ratio of 100:0 in the propositus as well as in five out of seven unaffected female relatives in four generations. The OCRL1 "de novo" mutation resides in the active paternally inherited X chromosome. X chromosome haplotype analysis suggests the presence of a locus for the familial skewed X inactivation in chromosome Xq25 most likely controlling X chromosome choice in X inactivation or cell proliferation. The description of this case adds Lowe syndrome to the list of X-linked disorders which may manifest the full phenotype in females because of the skewed X inactivation.

Abnormal X : autosome ratio, but normal X chromosome inactivation in human triploid cultures

Abstract: Background X chromosome inactivation (XCI) is that aspect of mammalian dosage compensation that brings about equivalence of X-linked gene expression between females and males by inactivating one of the two X chromosomes (Xi) in normal female cells, leaving them with a single active X (Xa) as in male cells. In cells with more than two X's, but a diploid autosomal complement, all X's but one, Xa, are inactivated. This phenomenon is commonly thought to suggest 1) that normal development requires a ratio of one Xa per diploid autosomal set, and 2) that an early event in XCI is the marking of one X to be active, with remaining X's becoming inactivated by default.

Dosage compensation of the X chromosome and Turner syndrome

Abstract: Turner patients have a karyotype of 45,X, while normal females are 46,XX and normal males are 46,XY. In order to understand Turner syndrome, it is important to understand how gene dosage of the X chromosome is regulated. In this review, we address sex chromosome evolution and the two forms of X chromosome dosage compensation: X upregulation and X inactivation. Recent microarray analyses have provided evidence for two-fold X upregulation in males and females. This equalizes gene dosage between the X chromosome and the autosomes. Inactivation of one of the two X chromosomes in females occurs to prevent functional tetrasomy and to equalize gene dosage between the sexes. However, 15–25% of human X-linked genes escape X inactivation. These escape genes are thought to contribute to the phenotype of Turner patients. Expression of escape genes is tissue-specific, suggesting that their role in Turner phenotypes is tissue-dependent. Recent data support a role for CTCF and chromatin structure in the regulation of genes that escape X inactivation.

MSL complex associates with clusters of actively transcribed genes along the Drosophila male X chromosome.

Abstract: Dosage compensation in Drosophila serves as a model system for understanding the targeting of chromatin-modifying complexes to their sites of action. The MSL (male-specific lethal) complex up-regulates transcription of the single male X chromosome, thereby equalizing levels of transcription of X-linked genes between the sexes. Recruitment of the MSL complex to its binding sites on the male X chromosome requires each of the MSL proteins and at least one of the two large noncoding roX RNAs. To better understand how the MSL complex specifically targets the X chromosome, we have defined the binding using high-resolution genomic tiling arrays. Our results indicate that the MSL complex largely associates with transcribed genes that are present in clusters along the X chromosome. We hypothesize that after initial recruitment of the MSL complex to the X chromosome by unknown mechanisms, nascent transcripts or chromatin marks associated with active transcription attract the MSL complex to its final targets. Defining MSL-complex-binding sites will provide a tool for understanding functions of large noncoding RNAs that have remained elusive.