Novel CpG-free vertebrate insulator: role for YY1

新型无 CpG 脊椎动物绝缘体:YY1 的作用

基本信息

  • 批准号:
    7991095
  • 负责人:
  • 金额:
    $ 7.7万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2010
  • 资助国家:
    美国
  • 起止时间:
    2010-08-01 至 2012-07-30
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Insulators are regulatory DNA sequences which form gene boundaries and protect genes from the influence of neighboring chromatin. Insulator-proteins bind to insulator DNA elements in the genome and tether those regions to subnuclear structures thus forming chromatin loops such that enhancer/silencer elements of one gene may not gain access to the promoter of a neighboring gene. Given the complexity of the human genome, one would expect that a variety of insulators and insulator- proteins regulate transcription of the estimated 35,000 genes. For example, in Drosophila alone, four types of insulators and binding proteins have been reported. In contrast, only one type of insulator (chicken globin HS4) and insulator-protein (CTCF) has been reported so far in vertebrates. CTCF mediated insulator activity is modulated by methylation of DNA. We have characterized a CpG-free, CTCF-independent vertebrate insulator (SP-10 insulator) from a testis-specific gene. The SP-10 insulator is conserved between mice and men. Preliminary mutation studies have indicated that transcription factor YY1 may mediate the SP-10 insulator function. In the proposed pilot study, we will investigate if YY1 interacts with the SP-10 insulator in vitro (using EMSA) and in a physiological context (using ChIP) (Specific Aim 1); and address the requirement of YY1 for SP-10 insulator function using RNAi in a cell culture model as well as a YY1 conditional knockout mouse model (Specific Aim 2). This feasibility study is a small self-contained research project with the potential to lead to a larger hypothesis-driven study. A recent study has shown that YY1 is essential for spermatogenesis. The current study will expand the role of YY1 to testis-specific gene transcription and in the long-term to male infertility. PUBLIC HEALTH RELEVANCE: Incidence of infertility is on the rise; it has been estimated that in the United States one in six couples in the reproductive age group are unable to conceive. The male factor contributes to 50% of the infertility cases. Treatment options are limited for men owing to a poor understanding of the mechanisms controlling sperm production (spermatogenesis). Here we propose to study the role of a transcription factor YY1 in regulating testis-specific gene transcription. Since the mouse model has recently shown that absence of YY1 in male germ cells leads to defective spermatogenesis, the proposed studies on the function of YY1 in testis are highly important for male infertility and are therefore of high public health relevance.
描述(由申请人提供):绝缘子是形成基因边界并保护基因免受邻近染色质影响的调控DNA序列。绝缘子蛋白与基因组中的绝缘子DNA元件结合,并将这些区域连接到亚核结构上,从而形成染色质环,使一个基因的增强子/沉默子元件无法进入邻近基因的启动子。考虑到人类基因组的复杂性,人们会期望各种各样的绝缘子和绝缘子蛋白调节着大约35000个基因的转录。例如,仅在果蝇中,就有四种类型的绝缘体和结合蛋白被报道。相比之下,迄今为止在脊椎动物中只报道了一种绝缘体(鸡珠蛋白HS4)和绝缘体蛋白(CTCF)。CTCF介导的绝缘子活性由DNA甲基化调节。我们已经从睾丸特异性基因中鉴定出不含cpg、不依赖ctcf的脊椎动物绝缘子(SP-10绝缘子)。SP-10绝缘体在老鼠和人之间是保守的。初步突变研究表明,转录因子YY1可能介导SP-10绝缘子功能。在拟议的试点研究中,我们将调查YY1是否在体外(使用EMSA)和生理环境下(使用ChIP)与SP-10绝缘体相互作用(具体目标1);并在细胞培养模型和YY1条件敲除小鼠模型中使用RNAi解决YY1对SP-10绝缘子功能的要求(Specific Aim 2)。这项可行性研究是一个小型的独立研究项目,有可能导致更大的假设驱动研究。最近的一项研究表明,YY1对精子形成至关重要。目前的研究将扩大YY1在睾丸特异性基因转录中的作用,并从长远来看对男性不育的影响。

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 }}

PRABHAKARA P REDDI其他文献

PRABHAKARA P REDDI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('PRABHAKARA P REDDI', 18)}}的其他基金

Generation of a new Cre-deleter mouse line to study spermiogenesis
生成新的 Cre-deleter 小鼠品系以研究精子发生
  • 批准号:
    10668012
  • 财政年份:
    2023
  • 资助金额:
    $ 7.7万
  • 项目类别:
RNA Pol II Pausing is Critical for Spermatogenesis and Male Fertility
RNA Pol II 暂停对于精子发生和男性生育能力至关重要
  • 批准号:
    10438669
  • 财政年份:
    2018
  • 资助金额:
    $ 7.7万
  • 项目类别:
RNA Pol II Pausing is Critical for Spermatogenesis and Male Fertility
RNA Pol II 暂停对于精子发生和男性生育能力至关重要
  • 批准号:
    9767846
  • 财政年份:
    2018
  • 资助金额:
    $ 7.7万
  • 项目类别:
RNA Pol II Pausing is Critical for Spermatogenesis and Male Fertility
RNA Pol II 暂停对于精子发生和男性生育能力至关重要
  • 批准号:
    10199764
  • 财政年份:
    2018
  • 资助金额:
    $ 7.7万
  • 项目类别:
Regulation of chromatin remodeling during spermiogenesis
精子发生过程中染色质重塑的调节
  • 批准号:
    8815702
  • 财政年份:
    2014
  • 资助金额:
    $ 7.7万
  • 项目类别:
Regulation of chromatin remodeling during spermiogenesis
精子发生过程中染色质重塑的调节
  • 批准号:
    8974424
  • 财政年份:
    2014
  • 资助金额:
    $ 7.7万
  • 项目类别:
Novel CpG-free vertebrate insulator: role for YY1
新型无 CpG 脊椎动物绝缘体:YY1 的作用
  • 批准号:
    8113359
  • 财政年份:
    2010
  • 资助金额:
    $ 7.7万
  • 项目类别:
Transcriptional Regulation During Spermiogenesis
精子发生过程中的转录调控
  • 批准号:
    7846302
  • 财政年份:
    2009
  • 资助金额:
    $ 7.7万
  • 项目类别:
Transcriptional Regulation During Spermiogenesis
精子发生过程中的转录调控
  • 批准号:
    6773455
  • 财政年份:
    1998
  • 资助金额:
    $ 7.7万
  • 项目类别:
TRANSCRIPTIONAL REGULATION DURING SPERMIOGENESIS
精子发生过程中的转录调控
  • 批准号:
    6125593
  • 财政年份:
    1998
  • 资助金额:
    $ 7.7万
  • 项目类别:

相似海外基金

Epigenetic mechanisms of tumor formation in Beckwith-wiedemann Syndrome
Beckwith-wiedemann 综合征肿瘤形成的表观遗传机制
  • 批准号:
    9813688
  • 财政年份:
    2019
  • 资助金额:
    $ 7.7万
  • 项目类别:
The Mechanism of Tumor Formation in Beckwith-Wiedemann Syndrome
Beckwith-Wiedemann 综合征的肿瘤形成机制
  • 批准号:
    9112963
  • 财政年份:
    2015
  • 资助金额:
    $ 7.7万
  • 项目类别:
The Mechanism of Tumor Formation in Beckwith-Wiedemann Syndrome
Beckwith-Wiedemann 综合征的肿瘤形成机制
  • 批准号:
    9307753
  • 财政年份:
    2015
  • 资助金额:
    $ 7.7万
  • 项目类别:
The relationship between paternal uniparental disomy and renal-urological features in patients with Beckwith-Wiedemann syndrome
Beckwith-Wiedemann综合征患者父亲单亲二体性与肾泌尿系统特征的关系
  • 批准号:
    23791186
  • 财政年份:
    2011
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Grant-in-Aid for Young Scientists (B)
Investigation of Imprinting mechanism between Beckwith-Wiedemann syndrome and Wilms tumor
Beckwith-Wiedemann综合征与肾母细胞瘤印记机制的研究
  • 批准号:
    22591986
  • 财政年份:
    2010
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Epigenomics studies in Beckwith-Wiedemann syndrome
Beckwith-Wiedemann 综合征的表观基因组学研究
  • 批准号:
    199064
  • 财政年份:
    2010
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Studentship Programs
Beckwith-Wiedemann syndrome and associated tumors - Identification of factors essential for imprinting mechanisms
Beckwith-Wiedemann 综合征和相关肿瘤 - 识别印记机制必需的因素
  • 批准号:
    36391329
  • 财政年份:
    2006
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Priority Programmes
Beckwith-Wiedemann syndrome and associated tumors: Identification of factors essential for imprinting mechanisms
Beckwith-Wiedemann 综合征和相关肿瘤:识别印记机制必需的因素
  • 批准号:
    5370882
  • 财政年份:
    2002
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Priority Programmes
Construction of model mouse of the Beckwith-wiedemann syndrome
Beckwith-wiedemann综合征小鼠模型的构建
  • 批准号:
    11670145
  • 财政年份:
    1999
  • 资助金额:
    $ 7.7万
  • 项目类别:
    Grant-in-Aid for Scientific Research (C)
Molecular mechanisms in beckwith wiedemann syndrome
Beckwith wiedemann 综合征的分子机制
  • 批准号:
    nhmrc : 981045
  • 财政年份:
    1998
  • 资助金额:
    $ 7.7万
  • 项目类别:
    NHMRC Project Grants
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了