X Chromosome

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Judith Wexler - One of the best experts on this subject based on the ideXlab platform.

  • the X Chromosome of the german cockroach blattella germanica is homologous to a fly X Chromosome despite 400 million years divergence
    BMC Biology, 2019
    Co-Authors: Richard P Meisel, Pablo J Delclos, Judith Wexler
    Abstract:

    SeX Chromosome evolution is a dynamic process that can proceed at varying rates across lineages. For eXample, different Chromosomes can be seX-linked between closely related species, whereas other seX Chromosomes have been conserved for > 100 million years. Cases of long-term seX Chromosome conservation could be informative of factors that constrain seX Chromosome evolution. Cytological similarities between the X Chromosomes of the German cockroach (Blattella germanica) and most flies suggest that they may be homologous—possibly representing an eXtreme case of long-term conservation. To test the hypothesis that the cockroach and fly X Chromosomes are homologous, we analyzed whole-genome sequence data from cockroaches. We found evidence in both sequencing coverage and heterozygosity that a significant eXcess of the same genes are on both the cockroach and fly X Chromosomes. We also present evidence that the candidate X-linked cockroach genes may be dosage compensated in hemizygous males. Consistent with this hypothesis, three regulators of transcription and chromatin on the fly X Chromosome are conserved in the cockroach genome. Our results support our hypothesis that the German cockroach shares the same X Chromosome as most flies. This may represent the convergent evolution of the X Chromosome in the lineages leading to cockroaches and flies. Alternatively, the common ancestor of most insects may have had an X Chromosome that resembled the eXtant cockroach and fly X. Cockroaches and flies diverged ∼ 400 million years ago, which would be the longest documented conservation of a seX Chromosome. Cockroaches and flies have different mechanisms of seX determination, raising the possibility that the X Chromosome was conserved despite the evolution of the seX determination pathway.

  • the X Chromosome of the german cockroach blattella germanica is homologous to a fly X Chromosome despite 400 million years divergence
    bioRxiv, 2018
    Co-Authors: Richard P Meisel, Judith Wexler
    Abstract:

    The Chromosomes that are seX-linked can differ between closely related species. Cases of long-term conservation could be informative of factors that prevent this seX Chromosome turnover. We analyzed whole genome sequence data and found that many of the same genes are on the German cockroach, Blattella germanica, X Chromosome and the ancestral X Chromosome of higher flies. We also show that three regulators of transcription and chromatin on the fly X Chromosome are conserved in the cockroach genome. We hypothesize that the common ancestor of cockroaches and flies had an X Chromosome that resembled the eXtant cockroach/fly X. Cockroaches and flies diverged ~400 million years ago, making this the longest documented conservation of a seX Chromosome. Cockroaches and most flies have different mechanisms of seX determination, suggesting long-term conservation of the X Chromosome despite evolution of the seX determination pathway.

Richard P Meisel - One of the best experts on this subject based on the ideXlab platform.

  • the X Chromosome of the german cockroach blattella germanica is homologous to a fly X Chromosome despite 400 million years divergence
    BMC Biology, 2019
    Co-Authors: Richard P Meisel, Pablo J Delclos, Judith Wexler
    Abstract:

    SeX Chromosome evolution is a dynamic process that can proceed at varying rates across lineages. For eXample, different Chromosomes can be seX-linked between closely related species, whereas other seX Chromosomes have been conserved for > 100 million years. Cases of long-term seX Chromosome conservation could be informative of factors that constrain seX Chromosome evolution. Cytological similarities between the X Chromosomes of the German cockroach (Blattella germanica) and most flies suggest that they may be homologous—possibly representing an eXtreme case of long-term conservation. To test the hypothesis that the cockroach and fly X Chromosomes are homologous, we analyzed whole-genome sequence data from cockroaches. We found evidence in both sequencing coverage and heterozygosity that a significant eXcess of the same genes are on both the cockroach and fly X Chromosomes. We also present evidence that the candidate X-linked cockroach genes may be dosage compensated in hemizygous males. Consistent with this hypothesis, three regulators of transcription and chromatin on the fly X Chromosome are conserved in the cockroach genome. Our results support our hypothesis that the German cockroach shares the same X Chromosome as most flies. This may represent the convergent evolution of the X Chromosome in the lineages leading to cockroaches and flies. Alternatively, the common ancestor of most insects may have had an X Chromosome that resembled the eXtant cockroach and fly X. Cockroaches and flies diverged ∼ 400 million years ago, which would be the longest documented conservation of a seX Chromosome. Cockroaches and flies have different mechanisms of seX determination, raising the possibility that the X Chromosome was conserved despite the evolution of the seX determination pathway.

  • the X Chromosome of the german cockroach blattella germanica is homologous to a fly X Chromosome despite 400 million years divergence
    bioRxiv, 2018
    Co-Authors: Richard P Meisel, Judith Wexler
    Abstract:

    The Chromosomes that are seX-linked can differ between closely related species. Cases of long-term conservation could be informative of factors that prevent this seX Chromosome turnover. We analyzed whole genome sequence data and found that many of the same genes are on the German cockroach, Blattella germanica, X Chromosome and the ancestral X Chromosome of higher flies. We also show that three regulators of transcription and chromatin on the fly X Chromosome are conserved in the cockroach genome. We hypothesize that the common ancestor of cockroaches and flies had an X Chromosome that resembled the eXtant cockroach/fly X. Cockroaches and flies diverged ~400 million years ago, making this the longest documented conservation of a seX Chromosome. Cockroaches and most flies have different mechanisms of seX determination, suggesting long-term conservation of the X Chromosome despite evolution of the seX determination pathway.

Edith Heard - One of the best experts on this subject based on the ideXlab platform.

  • Regulation of X-Chromosome inactivation by the X-inactivation centre
    Nature Reviews Genetics, 2011
    Co-Authors: Sandrine Augui, Elphège P. Nora, Edith Heard
    Abstract:

    X-Chromosome inactivation (XCI) ensures dosage compensation in mammals and is a paradigm for allele-specific gene eXpression on a Chromosome-wide scale. Important insights have been made into the developmental dynamics of this process. Recent studies have identified several cis- and trans-acting factors that regulate the initiation of XCI via the X-inactivation centre. Such studies have shed light on the relationship between XCI and pluripotency. They have also revealed the eXistence of dosage-dependent activators that trigger XCI when more than one X Chromosome is present, as well as possible mechanisms underlying the monoallelic regulation of this process. The recent discovery of the plasticity of the inactive state during early development, or during cloning, and induced pluripotency have also contributed to the X Chromosome becoming a gold standard in reprogramming studies.

  • dosage compensation in mammals fine tuning the eXpression of the X Chromosome
    Genes & Development, 2006
    Co-Authors: Edith Heard, Christine M Disteche
    Abstract:

    Mammalian females have two X Chromosomes and males have only one. This has led to the evolution of special mechanisms of dosage compensation. The inactivation of one X Chromosome in females equalizes gene eXpression between the seXes. This process of X-Chromosome inactivation (XCI) is a remarkable eXample of long-range, monoallelic gene silencing and facultative heterochromatin formation, and the questions surrounding it have fascinated biologists for decades. How does the inactivation of more than a thousand genes on one X Chromosome take place while the other X Chromosome, present in the same nucleus, remains genetically active? What are the underlying mechanisms that trigger the initial differential treatment of the two X Chromosomes? How is this differential treatment maintained once it has been established, and how are some genes able to escape the process? Does the mechanism of X inactivation vary between species and even between lineages? In this review, X inactivation is considered in evolutionary terms, and we discuss recent insights into the epigenetic changes and developmental timing of this process. We also review the discovery and possible implications of a second form of dosage compensation in mammals that deals with the unique, potentially haploinsufficient, status of the X Chromosome with respect to autosomal gene eXpression.

  • differential histone h3 lys 9 and lys 27 methylation profiles on the X Chromosome
    Molecular and Cellular Biology, 2004
    Co-Authors: Claire Rougeulle, Philip Avner, Julie Chaumeil, Kavitha Sarma, David C Allis, Danny Reinberg, Edith Heard
    Abstract:

    Histone H3 tail modifications are among the earliest chromatin changes in the X-Chromosome inactivation process. In this study we investigated the relative profiles of two important repressive marks on the X Chromosome: methylation of H3 lysine 9 (K9) and 27 (K27). We found that both H3K9 dimethylation and K27 trimethylation characterize the inactive X in somatic cells and that their relative kinetics of enrichment on the X Chromosome as it undergoes inactivation are similar. However, dynamic changes of H3K9 and H3K27 methylation on the inactivating X Chromosome compared to the rest of the genome are distinct, suggesting that these two modifications play complementary and perhaps nonredundant roles in the establishment and/or maintenance of X inactivation. Furthermore, we show that a hotspot of H3K9 dimethylation 5' to Xist also displays high levels of H3 tri-meK27. However, analysis of this region in G9a mutant embryonic stem cells shows that these two methyl marks are dependent on different histone methyltransferases.

  • recent advances in X Chromosome inactivation
    Current Opinion in Cell Biology, 2004
    Co-Authors: Edith Heard
    Abstract:

    X inactivation is the silencing one of the two X Chromosomes in XX female mammals. Initiation of this process during early development is controlled by the X-inactivation centre, a compleX locus that determines how many, and which, X Chromosomes will be inactivated. It also produces the Xist transcript, a remarkable RNA that coats the X Chromosome in cis and triggers its silencing. Xist RNA coating induces a cascade of chromatin changes on the X Chromosome, including the recruitment of Polycomb group proteins. This results in an inactive state that is initially labile, but may be further locked in by epigenetic marks such as DNA methylation. In mice, X inactivation has recently been found to be much more dynamic than previously thought during early pre-implantation development. The paternal X Chromosome is initially inactivated in all cells of cleavage-stage embryos and then selectively reactivated in the subset of cells that will form the embryo, with random X inactivation occurring thereafter.

  • X Chromosome inactivation counting choice and initiation
    Nature Reviews Genetics, 2001
    Co-Authors: Philip Avner, Edith Heard
    Abstract:

    In many seXually dimorphic species, a mechanism is required to ensure equivalent levels of gene eXpression from the seX Chromosomes. In mammals, such dosage compensation is achieved by X-Chromosome inactivation, a process that presents a unique medley of biological puzzles: how to silence one but not the other X Chromosome in the same nucleus; how to count the number of X's and keep only one active; how to choose which X Chromosome is inactivated; and how to establish this silent state rapidly and efficiently during early development. The key to most of these puzzles lies in a unique locus, the X-inactivation centre and a remarkable RNA — Xist — that it encodes.

Anton Wutz - One of the best experts on this subject based on the ideXlab platform.

Ian J. Deary - One of the best experts on this subject based on the ideXlab platform.

  • The influence of X Chromosome variants on trait neuroticism.
    Molecular Psychiatry, 2019
    Co-Authors: Michelle Luciano, Gail Davies, Kim M. Summers, W. David Hill, Caroline Hayward, David C. Liewald, David J. Porteous, Catharine R. Gale, Andrew M. Mcintosh, Ian J. Deary
    Abstract:

    Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately powered samples. But such studies have so far eXcluded the X Chromosome from analysis. Here, we report genetic association analyses of X Chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X Chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of the lead neuroticism-related X Chromosome variants were located in intergenic regions (n = 397). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X Chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.22% (SE = 0.05) from a full dosage compensation model. A polygenic X-variant score created in an independent sample (maXimum N ≈ 7,300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X Chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and compleX disorders.

  • The influence of X Chromosome variants on trait neuroticism.
    2018
    Co-Authors: Michelle Luciano, Gail Davies, Kim M. Summers, W. David Hill, Caroline Hayward, David C. Liewald, David J. Porteous, Catharine R. Gale, Andrew M. Mcintosh, Ian J. Deary
    Abstract:

    Autosomal variants have successfully been associated with trait neuroticism in genome-wide analysis of adequately-powered samples. But such studies have so far eXcluded the X Chromosome from analysis. Here, we report genetic association analyses of X Chromosome and XY pseudoautosomal single nucleotide polymorphisms (SNPs) and trait neuroticism using UK Biobank samples (N = 405,274). Significant association was found with neuroticism on the X Chromosome for 204 markers found within three independent loci (a further 783 were suggestive). Most of these significant neuroticism-related X Chromosome variants were located in intergenic regions (n = 713). Involvement of HS6ST2, which has been previously associated with sociability behaviour in the dog, was supported by single SNP and gene-based tests. We found that the amino acid and nucleotide sequences are highly conserved between dogs and humans. From the suggestive X Chromosome variants, there were 19 nearby genes which could be linked to gene ontology information. Molecular function was primarily related to binding and catalytic activity; notable biological processes were cellular and metabolic, and nucleic acid binding and transcription factor protein classes were most commonly involved. X-variant heritability of neuroticism was estimated at 0.34% (SE = 0.07). A polygenic X-variant score created in an independent sample (maXimum N ≈ 7300) did not predict significant variance in neuroticism, psychological distress, or depressive disorder. We conclude that the X Chromosome harbours significant variants influencing neuroticism, and might prove important for other quantitative traits and compleX disorders.