Aging and the evolution of the sex-specific chromatin structure in Drosophila

果蝇的衰老和性别特异性染色质结构的进化

• 批准号: 9564331
• 负责人: Doris Bachtrog
• 金额: $ 68.28万
• 依托单位: UNIVERSITY OF CALIFORNIA BERKELEY
• 依托单位国家: 美国
• 财政年份: 2017
• 资助国家: 美国
• 起止时间: 2017-09-30 至 2019-08-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9564331
• 关键词: Address; Adult; Age; Aging; Architecture; Automobile Driving; Biological Assay; Cardiovascular Diseases; Categories; Cause of Death; Cell Aging; Chromatin; Chromatin Structure; Chronic; Complement; DNA; DNA Transposable Elements; Data; Deterioration; Developed Countries; Developing Countries; Diabetes Mellitus; Disease; Drosophila genus; Epigenetic Process; Equilibrium; Euchromatin; Evolution; Female; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Genes; Genome; Global Change; Heterochromatin; Histones; Individual; Karyotype; Life; Link; Longevity; Maintenance; Malignant Neoplasms; Measures; Methods; Molecular Profiling; Pattern; Polycomb; Proteins; Repression; Role; Sampling; Series; Sex Chromosomes; Stroke; Techniques; Testing; Time; Tissues; X Chromosome; Y Chromosome; age related; aged; autosome; cell age; chromatin modification; dosage; fly; histone modification; male; mortality; next generation sequencing; overexpression; promoter; sex

Aging and the sex-specific chromatin in Drosophila The chromatin landscape is key for gene regulation, but little is known about how it differs between sexes, or over adult life. There is accumulating evidence that chromatin changes during an individual's lifespan contribute to cellular aging. In particular, loss of heterochromatin has been observed in aged cells of several species, including Drosophila. Age-specific mortality rates of male flies are higher and average lifespans are shorter than those of females. Males also contain substantially more heterochromatic DNA than females, due to the presence of a large, repeat-rich Y chromosome, and our preliminary data suggest that the presence of sex chromosomes with different epigenetic profiles in Drosophila (that is, a hyper-transcribed dosage compensated X chromosome, and a silenced heterochromatic Y) result in global changes of chromatin structure between sexes. We propose to compare sex-specific gene expression and epigenetic profiles in Drosophila species and strains with different sex chromosome karyotypes across their lifespan, to study the influence of sex- specific chromatin differences on cellular aging. We will experimentally modify protein levels of genes involved in heterochromatin maintenance, to directly test if heterochromatin formation is a main contributor to sex-specific epigenetic profiles and longevity. Additionally, we will assay chromatin states in time- series samples, and characterize tissue-specific chromatin states in aged vs. young flies, to address the temporal dynamics of changes in chromatin during aging, and potentially important differences in cellular aging across tissues.

果蝇中的衰老和性别特异性染色质 染色质景观是基因调节的关键，但对 它在性别之间或成年生活之间的差异。有积累的证据 在个体的寿命中，染色质改变有助于细胞 老化。特别是，在老年细胞中观察到异染色质的丧失 几种物种，包括果蝇。男性苍蝇的年龄特异性死亡率 比女性的寿命更高，平均寿命短。男性也是 由于 存在大型，重复的Y染色体，我们的初步数据表明 在具有不同表观遗传特征的性染色体中存在 果蝇（即一种超转录的剂量补偿X染色体， 并沉默的异质y）导致染色质结构的全局变化 在性别之间。我们建议比较性别特异性基因表达和 果蝇物种的表观遗传学特征和不同性别的菌株 在其寿命范围内染色体核型，以研究性别的影响 - 细胞衰老的特定染色质差异。我们将通过实验修改 参与异染色质维持的蛋白质水平，直接测试 如果异染色质形成是性别特异性表观遗传学的主要因素 概况和寿命。此外，我们将在时间上测定染色质状态 串联样品，表征了老化V的组织特异性染色质状态。 年轻的苍蝇，以解决染色质变化期间变化的时间动态 衰老，以及整个组织细胞衰老的潜在重要差异。