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.

衰老与果蝇性别特异性染色质 染色质景观是基因调控的关键，但人们对染色质景观知之甚少。 性别之间或成年生活中有何不同。越来越多的证据 在个体的一生中，染色质的变化有助于细胞 衰老特别是，在老年人的细胞中观察到异染色质的丢失， 包括果蝇在内的几个物种。雄蝇的特定年龄死亡率 比女性高，平均寿命短。雄性动物还 含有比女性更多的异染色质DNA，由于 存在一个大的，重复丰富的Y染色体，我们的初步数据表明， 具有不同表观遗传特征的性染色体的存在 果蝇（即超转录剂量补偿X染色体， 和沉默的异染色质Y）导致染色质结构的整体变化 两性之间。我们建议比较性别特异性基因表达， 不同性别果蝇种和品系的表观遗传图谱 染色体核型，来研究性别的影响， 细胞衰老的特殊染色质差异。我们将实验性地修改 蛋白质水平的基因参与异染色质的维持，直接测试 如果异染色质形成是性别特异性表观遗传的主要贡献者， 配置文件和寿命。另外，我们将及时检测染色质状态- 系列样品，并表征组织特异性染色质状态，在老化与 年轻的苍蝇，以解决染色质变化的时间动态， 老化，以及组织间细胞老化的潜在重要差异。