The formation of Heterochromatin on evolving Y chromosomes
The formation of Heterochromatin on evolving Y chromosomes
批准号:
10331018
负责人:
Doris Bachtrog
金额:
$41.92万
依托单位国家:
美国
项目类别:
财政年份:
2015
资助国家:
美国
项目状态:
已结题
起止时间:
2015-01-01 至 2023-03-31
关键词:
3-DimensionalAdoptedAppearanceArchitectureBindingBiological AssayCandidate Disease GeneCatalogingCatalogsCell physiologyCentromereChIP-seqChromatinChromatin StructureChromosomesCoupledDNADNA BindingDNA Transposable ElementsDataDepositionDevelopmentDiseaseDrosophila genusDrosophila melanogasterElementsEmbryoEpigenetic ProcessEuchromatinEukaryotaFemaleGene ExpressionGene Expression ProfileGene Expression RegulationGene SilencingGenesGenomeHeterochromatinHeterogeneityHi-CHuman GenomeImpairmentKnowledgeLinkMapsModelingMolecularPathway interactionsProteinsProtocols documentationRNARegulationRepetitive SequenceResolutionResourcesSequence AnalysisSex ChromatinSignal TransductionSiteSmall RNATherapeuticTimeTranscriptTransgenic OrganismsVariantWorkY ChromosomeZinc Fingerscomparativeexperimental studygenome integritygenome-widegenome-wide analysishistone modificationnanopromotersmall hairpin RNAspatiotemporaltelomeretemporal measurementzygote
中文摘要
大多数真核生物的基因组中都含有很高比例的转座子。异染色质--一种浓缩的染色质
在富含TES和其他重复元素的区域中发现的状态,对于沉默TES和保持TES的完整性非常重要
基因组。
真核生物基因组的很大一部分,包括Y染色体,是异染色质的,
UP主要由重复序列组成,具有独特的染色质结构
基因沉默。异染色区具有很高的重复含量,其特征是
组蛋白修饰,但定义特定染色体结构域的主要序列元素
作为异染色质组装的首选部位还没有被很好地理解。此外,最近的工作已经
结果表明,果蝇异染色质的组成和组织在空间上是
异质性和动态性,以及各种细胞途径和分子组成
遗传上的惰性异染色质,但只有这些成分的子集已被表征。
我们的提案旨在剖析顺式和反式作用的细胞机制
异染色质的形成,通过研究全基因组异染色质的形成
不同野生型和转基因果蝇品系和物种的早期发育。最新研究
提示小RNA⎯可能来源于转座元件(TES)⎯或特化
DNA结合的锌指蛋白有助于异染色质靶向。使用以下组合
比较序列分析、基因表达研究、小RNA图谱和CHIP-SEQ
跨发展的实验定位与异染色质相关的组蛋白修饰
基因组相互作用图,我们将表征全基因组的时空异质性
黑腹果蝇和米兰达果蝇发育过程中异染色质的建立
在早期发育的3D图中记录惰性染色质的建立和成熟。这
将揭示哪些序列作为非活性染色质的成核位置,以及沉默是如何
染色质遍布整个基因组。异染色质的最初建立是由RNA驱动的
以及母体沉积到受精卵中的蛋白质成分。我们将利用
丰富的黑腹果蝇资源用于研究早期胚胎异染色质的形成
母体沉积的候选基因参与发育过程中异染色质的建立
胚胎。
将我们的结果整合到AIMS中,将提供异染色质是如何在
早期胚胎,封闭染色质的最初建立是否按顺序进行
方式,以及它如何在基因组的重复区域传播。我们将剖析
果蝇发育过程中异染色质的异质性和动态组成
使用转基因技术去除异染色质途径成分的胚胎
接近了。这将提供各种分子途径和不同的
参与产生遗传惰性异染色质的分子成分。
英文摘要
Most eukaryotes harbor a high proportion of transposable elements (TEs) in their genomes. Heterochromatin, a condensed chromatin
state found at domains enriched for TEs and other repetitious elements, is important for silencing TEs and maintaining the integrity of the
genome.
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. In addition, recent work has
shown that the composition and organization of Drosophila heterochromatin is spatially
heterogeneous and dynamic, and a variety of cellular pathways and molecular components create
genetically inert heterochromatin, but only a subset of these components has been characterized.
Our proposal aims to dissect the cis- and trans-acting cellular mechanisms involved in
heterochromatin formation, by studying the genome-wide establishment of heterochromatin during
early development in different wildtype and transgenic Drosophila strains and species. Recent studies
suggest that small RNAs ⎯ possibly derived from transposable elements (TEs) ⎯ or specialized
DNA-binding zinc finger proteins contribute to heterochromatin targeting. Using a combination of
comparative sequence analysis, gene expression studies, small RNA profiling and ChIP-seq
experiments across development to map histone modifications associated with heterochromatin and
genome interaction maps, we will characterize the spatiotemporal heterogeneity of genome-wide
heterochromatin establishment across development in Drosophila melanogaster and D. miranda, and
catalog the establishment and maturation of inert chromatin in 3D during early development. This
will reveal which sequences serve as nucleation sites for inactive chromatin, and how silencing
chromatin spreads across the genome. The initial establishment of heterochromatin is driven by RNA
and protein components that are maternally deposited into the fertilized egg. We will utilize the
wealth of D. melanogaster resources to study heterochromatin formation in early embryos by depleting
maternally deposited candidate genes involved in establishing heterochromatin in the developing
embryo.
Integrating our results across aims will provide a full picture of how heterochromatin is established in
the early embryo, whether the initial establishment of closed chromatin proceeds in a sequential
manner, and how it spreads across the repetitive regions of the genome. We will dissect the
heterogeneous and dynamic composition of Drosophila heterochromatin across development and in
embryos where components of the heterochromatin pathway are depleted using transgenic
approaches. This will provide a full picture of the various molecular pathways and different
molecular components involved in creating genetically inert heterochromatin.
期刊论文(0)
专著(0)
科研奖励(0)
会议论文
Aging and the evolution of the sex-specific chromatin structure in Drosophila
-
批准号:9564331
-
项目类别:
-
资助金额:$68.28万
-
财政年份:2017
-
负责人:Doris Bachtrog
-
依托单位:
Heterochromatin and Toxic YChromosomes
-
批准号:10521889
-
项目类别:
-
资助金额:$38.48万
-
财政年份:2015
-
负责人:Doris Bachtrog
-
依托单位:
The formation of Heterochromatin on evolving Y chromosomes
-
批准号:8991068
-
项目类别:
-
资助金额:$42.04万
-
财政年份:2015
-
负责人:Doris Bachtrog
-
依托单位:
The formation of Heterochromatin on evolving Y chromosomes
-
批准号:9398132
-
项目类别:
-
资助金额:$42.04万
-
财政年份:2015
-
负责人:Doris Bachtrog
-
依托单位:
"Gene Trafficking on an Evolving X Chromosome in Drosophila"
-
批准号:8231546
-
项目类别:
-
资助金额:$29.21万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
Comparative genomics of sex chromosomes in Diptera: gene trafficking, dosage comp
-
批准号:8898095
-
项目类别:
-
资助金额:$38.23万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
"Gene Trafficking on an Evolving X Chromosome in Drosophila"
-
批准号:8436307
-
项目类别:
-
资助金额:$28.19万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
Comparative genomics of sex chromosomes in Diptera: gene trafficking, dosage comp
-
批准号:8698035
-
项目类别:
-
资助金额:$38.12万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
"Gene Trafficking on an Evolving X Chromosome in Drosophila"
-
批准号:7866777
-
项目类别:
-
资助金额:$29.51万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
"Gene Trafficking on an Evolving X Chromosome in Drosophila"
-
批准号:8037078
-
项目类别:
-
资助金额:$29.21万
-
财政年份:2010
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7014718
-
项目类别:
-
资助金额:$22.23万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7391157
-
项目类别:
-
资助金额:$19.44万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7848509
-
项目类别:
-
资助金额:$2.12万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7201664
-
项目类别:
-
资助金额:$21.59万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
Dosage compensation and the rewiring of regulatory netoworks in Drosophila
-
批准号:9312026
-
项目类别:
-
资助金额:$31.4万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7897765
-
项目类别:
-
资助金额:$22.43万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
Dosage compensation and the rewiring of regulatory netoworks in Drosophila
-
批准号:9908079
-
项目类别:
-
资助金额:$31.33万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The evolution of dosage compensation in Drosophila
-
批准号:7612070
-
项目类别:
-
资助金额:$22.66万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The Evolutionary and Functional Genomics of Dosage Compensation in Drosophila
-
批准号:8911326
-
项目类别:
-
资助金额:$30.26万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
The Evolutionary and Functional Genomics of Dosage Compensation in Drosophila
-
批准号:8446473
-
项目类别:
-
资助金额:$29.2万
-
财政年份:2006
-
负责人:Doris Bachtrog
-
依托单位:
海外基金