Heterochromatin and Toxic YChromosomes

异染色质和有毒 Y 染色体

基本信息

批准号：
10521889
负责人：
Doris Bachtrog
金额：
$ 38.48万
依托单位：
UNIVERSITY OF CALIFORNIA BERKELEY
依托单位国家：
美国
项目类别：
财政年份：
2015
资助国家：
美国
起止时间：
2015-01-01 至 2027-01-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10521889
关键词：
Age Biological Assay Catalogs Cell physiology Centromere ChIP-seq Chromatin Chromatin Conformation Capture and Sequencing Chromatin Structure Chromosomes Code Conflict (Psychology)DNA DNA Insertion Elements DNA Transposable Elements Data Deterioration Development Disease Drosophila genus Elements Epigenetic Process Essential Genes Euchromatin Evolution Expression Profiling Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Transcription Genome Heterochromatin Hi-C Histones Human Genome Impairment Individual Libraries Link Longevity Modeling Modification Molecular Mutation Organism Phenotype Proteins Repetitive Sequence Resolution Selfish Genes Sex Chromatin Sex Chromosomes Testis Therapeutic Time Tissues Toxic effect Transcriptional Silencer Elements Work Y Chromosome autosome cost density fitness fly genome resource genomic locus histone modification male nanopore next generation sequencing novel strategies sex single molecule telomere transcriptome sequencing

Age Biological Assay Catalogs Cell physiology Centromere ChIP-seq Chromatin Chromatin Conformation Capture and Sequencing Chromatin Structure Chromosomes Code Conflict (Psychology)DNA DNA Insertion Elements DNA Transposable Elements Data Deterioration Development Disease Drosophila genus Elements Epigenetic Process Essential Genes Euchromatin Evolution Expression Profiling Gene Expression Gene Expression Profile Gene Expression Regulation Genes Genetic Transcription Genome Heterochromatin Hi-C Histones Human Genome Impairment Individual Libraries Link Longevity Modeling Modification Molecular Mutation Organism Phenotype Proteins Repetitive Sequence Resolution Selfish Genes Sex Chromatin Sex Chromosomes Testis Therapeutic Time Tissues Toxic effect Transcriptional Silencer Elements Work Y Chromosome autosome cost density fitness fly genome resource genomic locus histone modification male nanopore next generation sequencing novel strategies sex single molecule telomere transcriptome sequencing

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项目摘要

Y chromosomes of many organisms contain a large number of transposable elements (TEs), which are transcriptionally constrained by repressive chromatin marks. When relieved of these epigenetic modifications, many TEs can readily move from one genomic location to another (toxic Y chromosomes). Yet evolutionarily young Y chromosomes still contain a large number of essential genes that are actively transcribed, and competition between the opposing mechanisms of heterochromatin formation and active transcription can result in incomplete silencing of TEs on evolving Y chromosomes. Our proposal aims to characterize epigenetic conflicts between host-specific genes and selfish genetic elements on evolving Y chromosomes at various stages of degeneration, whose resolution may select for adaptive degeneration of the Y. The accumulation of repetitive elements on the Y chromosome appears to be universal during sex chromosome evolution. We will take advantage of evolving neo-Y chromosomes in Drosophila with varying levels of degeneration, to catalog toxicity of Y chromosomes using expression profiling and chromatin analysis. We will link epigenetic and expression profiles across neo-Y chromosomes that differ in gene and repeat density, to identify whether active transcription of genes on neo-Y chromosomes results in incomplete silencing of TEs. We will establish whether toxic Y chromosomes incur a fitness cost on males, by forming a mutational burden and reducing male longevity, as suggested by our preliminary work. Integrating our results across aims will provide a full picture of how the toxicity of the Y chromosome changes over time, and how epigenetic conflicts between host genes and selfish elements may be resolved.

许多生物的Y染色体包含大量可旋转元素（TES），在转录上受到抑制性染色质标记的约束。解除这些表观遗传学修改，许多TE可以很容易地从一个基因组位置移动到另一个基因组位置（有毒Y 染色体）。然而，进化上年轻的Y染色体仍然包含大量必需品积极转录的基因，以及相反机制之间的竞争异染色质形成和主动转录可能导致TES上的TES不完整不断发展的Y染色体。我们的建议旨在表征宿主特定基因与自私遗传之间的表观遗传冲突关于在各个变性阶段不断发展的Y染色体的元素，其分辨率可以选择 Y。Y。重复元素在Y染色体上的积累似乎是通用的染色体进化。我们将利用与果蝇中发展的新染色体变化水平的变化，使用表达谱和Y染色体的目录毒性和染色质分析。我们将在新染色体上将表观遗传和表达谱连接起来基因和重复密度有所不同，以确定基因在新Y上的主动转录是否染色体导致TES不完全沉默。我们将确定是否有毒Y染色体通过形成突变负担并降低男性长寿，以对男性产生健身成本由我们的初步工作建议。将我们的结果整合到跨目标将提供 Y染色体的毒性如何随着时间而变化，以及宿主之间的表观遗传冲突如何基因和自私元素可以解决。