Epigenetic control of sex chromosome behavior in meiosis.

减数分裂中性染色体行为的表观遗传控制。

基本信息

  • 批准号:
    8710279
  • 负责人:
  • 金额:
    $ 28.48万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2013
  • 资助国家:
    美国
  • 起止时间:
    2013-08-05 至 2017-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Meiosis is a special type of cell division that produces haploid gametes for sexual reproduction. During meiosis, chromosome pairing, synapsis and crossing over rely on homology between the paternal and maternal homologous chromosomes to ensure proper segregation and formation of gametes with the correct number of chromosomes. Crossovers are initiated by the formation and repair of induced double-strand breaks (DSBs) by homologous recombination. Defects in chromosome pairing disrupt DSB repair and result in checkpoint activation, leading to either apoptosis or the formation of aneuploid gametes. In males, sex chromosomes are largely hemizygous (i.e., lack a homologous chromosome), which presents a special challenge to repair DSBs and, moreover, to evade checkpoint activation. Our preliminary results show that DSB repair and checkpoint suppression occur in the context of a specialized chromatin structure found only on the X chromosome of males. Our overall hypothesis is that the epigenetic landscape of sex chromosomes and other aspects of male meiosis alter interactions with DSB repair and checkpoint machinery to ensure accurate transmission of the male genome through meiosis. To test this hypothesis we propose to elucidate the conserved mechanisms underlying chromosome behavior during male meiosis using the metazoan animal model Caenorhabditis elegans, which is particularly amenable to genetic, cell biological and molecular approaches. In Aim 1 we will define the pathways that mediate DSB repair on hemizygous regions of sex chromosomes by analyzing repair of both meiotic and engineered DSBs cytologically, molecularly and functionally in wild type and repair-defective mutants. In Aim 2 we will elucidate the role of specific histone modifications on DSB repair and checkpoint silencing by analyzing the recruitment of DSB processing factors and checkpoint proteins to DSBs in germ lines with altered chromatin. Here we will also probe the physical interactions between chromatin, chromatin modifiers, DNA repair and checkpoint proteins. In Aim 3 we will define global differences in DSB processing in the male versus female germ line. Together, an understanding of these processes in this genetically tractable system will provide novel and important insights into how the meiotic program is modified to promote successful male meiosis. These studies have direct relevance to understanding the increased frequency of sex chromosome aneuploidy associated with human meiosis resulting in developmental disorders including Turner and Klinefelter's Syndromes. Importantly, these studies will also elucidate general mechanisms of DNA repair and checkpoint signaling, which play critical roles in monitoring and maintaining genome integrity in all cells.
描述(由申请人提供):减数分裂是一种特殊类型的细胞分裂,产生用于有性生殖的单倍体配子。在减数分裂过程中,染色体配对、突触和交叉依赖于父本和母本同源染色体之间的同源性,以确保正确分离和形成具有正确数量染色体的配子。交叉是通过同源重组诱导双链断裂 (DSB) 的形成和修复来启动的。染色体配对缺陷会破坏 DSB 修复并导致检查点激活,从而导致细胞凋亡或非整倍体配子的形成。在男性中,性染色体大部分是半合子(即缺乏同源染色体),这对修复 DSB 以及逃避检查点激活提出了特殊的挑战。我们的初步结果表明,DSB 修复和检查点抑制发生在仅在男性 X 染色体上发现的特殊染色质结构的背景下。我们的总体假设是,性染色体的表观遗传景观和雄性减数分裂的其他方面改变了与 DSB 修复和检查点机制的相互作用,以确保雄性基因组通过减数分裂的准确传递。为了检验这一假设,我们建议使用后生动物模型秀丽隐杆线虫来阐明雄性减数分裂过程中染色体行为的保守机制,该模型特别适合遗传、细胞生物学和分子方法。在目标 1 中,我们将通过分析野生型和修复缺陷突变体中减数分裂和工程 DSB 的细胞学、分子和功能修复来定义介导性染色体半合子区域 DSB 修复的途径。在目标 2 中,我们将通过分析染色质改变的种系中 DSB 加工因子和检查点蛋白向 DSB 的募集情况,阐明特定组蛋白修饰对 DSB 修复和检查点沉默的作用。在这里,我们还将探讨染色质、染色质修饰剂、DNA 修复和检查点蛋白之间的物理相互作用。在目标 3 中,我们将定义雄性与雌性种系 DSB 处理的总体差异。总之,对这个遗传易处理系统中这些过程的理解将为如何修改减数分裂程序以促进成功的雄性减数分裂提供新颖且重要的见解。这些研究与了解与人类减数分裂相关的性染色体非整倍体频率增加有直接关系,导致包括特纳和克兰费尔特综合症在内的发育障碍。重要的是,这些研究还将阐明 DNA 修复和检查点信号传导的一般机制,这些机制在监测和维持所有细胞的基因组完整性方面发挥着关键作用。

项目成果

期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

数据更新时间:{{ journalArticles.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ monograph.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ sciAawards.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ conferencePapers.updateTime }}

{{ item.title }}
  • 作者:
    {{ item.author }}

数据更新时间:{{ patent.updateTime }}

JOANNE ENGEBRECHT其他文献

JOANNE ENGEBRECHT的其他文献

{{ item.title }}
{{ item.translation_title }}
  • DOI:
    {{ item.doi }}
  • 发表时间:
    {{ item.publish_year }}
  • 期刊:
  • 影响因子:
    {{ item.factor }}
  • 作者:
    {{ item.authors }}
  • 通讯作者:
    {{ item.author }}

{{ truncateString('JOANNE ENGEBRECHT', 18)}}的其他基金

Sex-specific regulation of meiosis
减数分裂的性别特异性调节
  • 批准号:
    9900011
  • 财政年份:
    2013
  • 资助金额:
    $ 28.48万
  • 项目类别:
Epigenetic control of sex chromosome behavior in meiosis.
减数分裂中性染色体行为的表观遗传控制。
  • 批准号:
    8577755
  • 财政年份:
    2013
  • 资助金额:
    $ 28.48万
  • 项目类别:
Analysis of checkpoint function in the germ line.
种系检查点功能分析。
  • 批准号:
    7930683
  • 财政年份:
    2009
  • 资助金额:
    $ 28.48万
  • 项目类别:
Cell Signaling in Meiosis
减数分裂中的细胞信号转导
  • 批准号:
    6915762
  • 财政年份:
    2002
  • 资助金额:
    $ 28.48万
  • 项目类别:
Cell Signaling in Meiosis
减数分裂中的细胞信号转导
  • 批准号:
    6604278
  • 财政年份:
    2002
  • 资助金额:
    $ 28.48万
  • 项目类别:
Cell Signaling in Meiosis
减数分裂中的细胞信号转导
  • 批准号:
    6530418
  • 财政年份:
    2002
  • 资助金额:
    $ 28.48万
  • 项目类别:
Cell Signaling in Meiosis
减数分裂中的细胞信号转导
  • 批准号:
    6771014
  • 财政年份:
    2002
  • 资助金额:
    $ 28.48万
  • 项目类别:
GENETIC ANALYSIS OF MEIOTIC CHROMOSOME SEGREGATION
减数分裂染色体分离的遗传分析
  • 批准号:
    2186147
  • 财政年份:
    1993
  • 资助金额:
    $ 28.48万
  • 项目类别:
GENETIC ANALYSIS OF MEIOTIC CHROMOSOME SEGREGATION
减数分裂染色体分离的遗传分析
  • 批准号:
    2186148
  • 财政年份:
    1993
  • 资助金额:
    $ 28.48万
  • 项目类别:
GENETIC ANALYSIS OF MEIOTIC CHROMOSOME SEGREGATION
减数分裂染色体分离的遗传分析
  • 批准号:
    3469004
  • 财政年份:
    1993
  • 资助金额:
    $ 28.48万
  • 项目类别:

相似海外基金

Quantification of Neurovasculature Changes in a Post-Hemorrhagic Stroke Animal-Model
出血性中风后动物模型中神经血管变化的量化
  • 批准号:
    495434
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
Small animal model for evaluating the impacts of cleft lip repairing scar on craniofacial growth and development
评价唇裂修复疤痕对颅面生长发育影响的小动物模型
  • 批准号:
    10642519
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
Bioactive Injectable Cell Scaffold for Meniscus Injury Repair in a Large Animal Model
用于大型动物模型半月板损伤修复的生物活性可注射细胞支架
  • 批准号:
    10586596
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
A Comparison of Treatment Strategies for Recovery of Swallow and Swallow-Respiratory Coupling Following a Prolonged Liquid Diet in a Young Animal Model
幼年动物模型中长期流质饮食后吞咽恢复和吞咽呼吸耦合治疗策略的比较
  • 批准号:
    10590479
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
Diurnal grass rats as a novel animal model of seasonal affective disorder
昼夜草鼠作为季节性情感障碍的新型动物模型
  • 批准号:
    23K06011
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Longitudinal Ocular Changes in Naturally Occurring Glaucoma Animal Model
自然发生的青光眼动物模型的纵向眼部变化
  • 批准号:
    10682117
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
A whole animal model for investigation of ingested nanoplastic mixtures and effects on genomic integrity and health
用于研究摄入的纳米塑料混合物及其对基因组完整性和健康影响的整体动物模型
  • 批准号:
    10708517
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
A Novel Large Animal Model for Studying the Developmental Potential and Function of LGR5 Stem Cells in Vivo and in Vitro
用于研究 LGR5 干细胞体内外发育潜力和功能的新型大型动物模型
  • 批准号:
    10575566
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
Elucidating the pathogenesis of a novel animal model mimicking chronic entrapment neuropathy
阐明模拟慢性卡压性神经病的新型动物模型的发病机制
  • 批准号:
    23K15696
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
The effect of anti-oxidant on swallowing function in an animal model of dysphagia
抗氧化剂对吞咽困难动物模型吞咽功能的影响
  • 批准号:
    23K15867
  • 财政年份:
    2023
  • 资助金额:
    $ 28.48万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了