The formation of Heterochromatin on evolving Y chromosomes

进化中的 Y 染色体上异染色质的形成

• 批准号: 9398132
• 负责人: Doris Bachtrog
• 金额: $ 42.04万
• 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 2018-12-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/9398132
• 关键词: Address; Appearance; Bacterial Artificial Chromosomes; Boundary Elements; Categories; Cell physiology; Centromere; ChIP-seq; Chromatin; Chromatin Structure; Chromosomes; Chromosomes, Human, 13-15; Code; DNA; DNA Sequence; DNA Transposable Elements; Data; Development; Disease; Drosophila genus; Elements; Epigenetic Process; Evolution; Expression Profiling; Gene Expression; Gene Expression Profile; Gene Expression Regulation; Gene Silencing; Genes; Genetic Transcription; Genome; Genomic approach; Genomics; Heterochromatin; Heterogeneity; Histones; Human Genome; Impairment; In Situ Hybridization; Larva; Libraries; Link; Location; Maps; Modeling; Molecular; Nature; Process; Proteins; Pseudogenes; Repetitive Sequence; Resources; Sequence Analysis; Sex Chromatin; Sex Chromosomes; Shotguns; Signal Transduction; Site; Small RNA; System; Therapeutic; Time; Y Chromosome; autosome; comparative; comparative genomics; experimental study; functional genomics; genome sequencing; genome-wide; histone modification; improved; next generation sequencing; public health relevance; scaffold; sex; spatiotemporal; telomere; three dimensional structure; transcriptome; transcriptome sequencing

DESCRIPTION (provided by applicant): Significant portions of eukaryotic genomes, including the Y chromosome, are heterochromatic, made up largely of repetitive sequences and possessing a distinctive chromatin structure associated with gene silencing. Heterochromatic regions have a high repeat content and are characterized by specific histone modifications, but the primary sequence elements that define specific chromosomal domains as preferred sites of heterochromatin assembly are not well understood. Recent studies suggest that small RNAs -- possibly derived from transposable elements (TEs) -- contribute to heterochromatin targeting. The recently formed neo-Y chromosomes of Drosophila albomicans and D. miranda are in the process of evolving altered chromatin structure: On the D. miranda neo-Y - which was formed about 1 MY ago - large segments have already acquired a heterochromatic appearance and TEs show a striking accumulation. About half of the neo-Y-loci have become non-functional, and most genes (<80%) are down-regulated from the neo-Y. This is supporting a link between heterochromatin formation and repetitive DNA, and its repressive effect on gene expression. The much younger D. albomicans neo-Y (<0.1 MY old) is mostly euchromatic, and most genes are functional on the neo-Y (<2% pseudogenes). However, almost 30% of neo-Y genes are down-regulated and in situ hybridization experiments reveal some early signs of accumulation of heterochromatin on the neo-Y of D. albomicans. D. miranda and D. albomicans therefore provide unique systems to study the mechanisms and evolution of heterochromatin formation in action using evolutionary approaches. Using a combination of comparative sequence analysis, gene expression studies, small RNA profiling and ChIP-seq experiments to map histone modifications associated with heterochromatin and genome interaction maps, we will address the following questions: What are the primary sequence elements used for targeting heterochromatin? Are small RNAs involved in heterochromatin targeting? What is the influence of heterochromatin formation on levels of gene expression? How far does heterochromatin spread in cis or in 3D? Is a high repeat content necessary for spreading of heterochromatin? Have chromatin boundary elements evolved on the neo-Y to limit spreading, and what is their molecular nature? Are histone modifications associated with active transcription counteracting the spread of heterochromatin? Can we identify other DNA sequence elements functioning as boundary elements on the neo-Y? Are certain categories of genes more likely to be heterochromatic? It will allow us to study the molecular basis of heterochromatin and how it evolves.

描述（由申请人提供）：真核基因组的重要部分，包括 Y 染色体，是异染色质的，主要由重复序列组成，并具有与基因沉默相关的独特染色质结构。异染色质区域具有高重复含量，并以特定的组蛋白修饰为特征，但将特定染色体结构域定义为异染色质组装的首选位点的一级序列元件尚不清楚。最近的研究表明，小 RNA（可能源自转座元件 (TE)）有助于异染色质靶向。白果蝇和米兰达果蝇最近形成的新 Y 染色体正处于进化改变染色质结构的过程中：在米兰达果蝇 Neo-Y 上（大约 1 年前形成），大片段已经获得了异染色质外观，并且TE 显示出惊人的积累。大约一半的 neo-Y 位点已变得无功能，并且大多数基因 (<80%) 均从 neo-Y 下调。这支持了异染色质形成和重复DNA之间的联系及其对基因表达的抑制作用。年轻得多的 D. albomicans neo-Y（<0.1 MY old）大多是常染色质，大多数基因在 neo-Y 上有功能（<2% 假基因）。然而，近 30% 的 neo-Y 基因被下调，原位杂交实验揭示了白色 D. albomicans 的 neo-Y 上异染色质积累的一些早期迹象。因此，D. miranda 和 D. albomicans 提供了独特的系统来使用进化方法研究异染色质形成的机制和进化。结合比较序列分析、基因表达研究、小 RNA 分析和 ChIP-seq 实验来绘制与异染色质相关的组蛋白修饰和基因组相互作用图谱，我们将解决以下问题：用于靶向异染色质的主要序列元件是什么？小RNA是否参与异染色质靶向？异染色质形成对基因表达水平有何影响？异染色质在顺式或 3D 中扩散多远？异染色质的扩散需要高重复含量吗？ Neo-Y 上的染色质边界元素是否进化来限制扩散？它们的分子性质是什么？与活性转录相关的组蛋白修饰是否会抵消异染色质的扩散？我们能否识别出在 neo-Y 上充当边界元素的其他 DNA 序列元素？某些类别的基因是否更有可能是异色的？它将使我们能够研究异染色质的分子基础及其演化方式。