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）：包括Y染色体在内的真核基因组的重要部分是杂色的，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。杂色区域具有较高的重复含量，并以特定的组蛋白修饰为特征，但是将特定的染色体结构域定义为异染色质组装的首选位点的主要序列元素尚不很好地理解。最近的研究表明，小RNA（可能来自转座元素（TES））有助于异染色质靶向。最近形成的果蝇和米兰达果蝇的新染色体正在进化改变的染色质结构：在D. miranda neo -y-上，它是我的前1个以前形成的 - 大片段已经获得了杂色的外观，并且表现出了惊人的积累。大约一半的Neo-Y-Loci已成为非功能性，大多数基因（<80％）从Neo-Y中下调。这支持了异染色质形成与重复DNA之间的联系，以及其对基因表达的抑制作用。年轻的D. bomicans neo-Y（<0.1我的旧）主要是正式的，大多数基因在Neo-Y上起作用（<2％的假基因）。然而，几乎30％的新基因被下调，原位杂交实验揭示了异染色质在白念珠菌的新染色质上积累的一些早期迹象。 D. Miranda和D. Albomicans提供了独特的系统来研究使用进化方法在作用中形成异染色质的机理和演变。使用比较序列分析，基因表达研究，小的RNA分析和芯片seq实验的组合来绘制与异染色质和基因组相互作用图相关的组蛋白修饰，我们将解决以下问题：用于靶向异染色质的主要序列元素是什么？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的影响是什么？异染色质在顺式或3D中传播多远？散布异染色质是否需要高的重复内容？染色质边界元素是否在新Y上演变以限制扩散，它们的分子性质是什么？与主动转录相关的组蛋白修饰是否抵消异染色质的扩散？我们可以识别其他DNA序列元件在NEO-Y上起边界元素的作用吗？某些类别的基因是否更有可能是异性的？它将使我们能够研究异染色质的分子基础及其演变。