Heterochromatin and Toxic YChromosomes

异染色质和有毒 Y 染色体

• 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
• 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

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染色体含有大量的转座因子（TE）， 在转录上受到抑制性染色质标记的限制。当这些表观遗传的 由于基因修饰，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（毒性Y 染色体）。然而，进化上年轻的Y染色体仍然含有大量的必需的 积极转录的基因，以及相反机制之间的竞争， 异染色质形成和活性转录可导致细胞上TE的不完全沉默， 进化出Y染色体 我们的建议旨在描述宿主特异性基因和自私遗传基因之间的表观遗传冲突， 在退化的各个阶段，进化的Y染色体上的元素，其分辨率可以选择 Y染色体的适应性退化 Y染色体上重复元件的积累似乎在性行为中是普遍的 染色体进化我们将利用果蝇新Y染色体的进化， 不同程度的变性，使用表达谱对Y染色体的毒性进行分类， 染色质分析我们将在新Y染色体上连接表观遗传和表达谱， 不同的基因和重复密度，以确定是否在neo-Y基因转录活跃 染色体导致TE的不完全沉默。我们将确定是否有毒的Y染色体 通过形成突变负担和减少雄性寿命， 这是我们初步工作的结果。将我们的结果整合到各个目标中将提供一个完整的画面， Y染色体的毒性如何随着时间的推移而变化，以及宿主之间的表观遗传冲突 基因和自私的因素可以解决。