EFFECTOR CD4 T CELL DEVELOPMENT
效应 CD4 T 细胞开发
基本信息
- 批准号:6228739
- 负责人:
- 金额:$ 30万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2001
- 资助国家:美国
- 起止时间:2001-01-01 至 2005-12-31
- 项目状态:已结题
- 来源:
- 关键词:
项目摘要
DESCRIPTION (Applicant's Abstract): We have found that in CD4 T lymphocytes,
the gene on chromosome 11 encoding interleukin-4 can be expressed in an
allelically-independent fashion and that the allelic pattern of expression
(mono-allelic or biallelic) can be heritably transmitted from parent to
daughter cell through an epigenetic mechanism. In a separate study, we have
identified dice (determinant of IL-4 commitment), a quantitative trait locus on
mouse chromosome 16, implicated in determining the proportion of recently
activated CD4 T-cells that commit to IL-4 production. We have speculated that
independent allelic regulation of the IL-4 gene may be a byproduct of a
mechanism evolved to impart an element of probability to its expression. This
proposal has three aims united by the long-term goal of understanding the
biological function of allelically-independent and epigenetically heritable
cytokine gene expression and to discover the molecular mechanisms responsible
for this process. First, we will identify trans and cis genetic determinants of
independent allelic activation of the IL-4 locus by addressing the following
hypotheses: la) The probability a given IL-4 allele will be activated is
genetically determined. 1b) dice is a trans determinant of the probability of
IL-4 allelic activation. 2) The probability of IL-4 allelic activation is
influenced by genetic elements that act in cis. 3) The probability of allelic
activation at the IL-4 locus influences the probability of allelic activation
at neighboring loci. Second, we will determine the structural correlates of
independent allelic activation of the IL-4 locus by studying long-term
antigen-specific CD4 T-cell clones to address the following hypotheses: 1) IL-4
allelic activation correlates with the appearance of allele-specific DNAse I
hypersensitive sites. 2) IL-4 allelic activation correlates with
allele-specific demethylation. Finally, we will resolve the genetic interval on
mouse chromosome 16 that contains dice to approximately 0.2 cM to lay the
groundwork for and establish the feasibility of cloning dice by position and
functional rescue.
描述(申请人摘要):我们发现在CD4T淋巴细胞中,
11号染色体上编码白介素4的基因可以在
等位基因独立的时尚和表达的等位基因模式
(单等位基因或双等位基因)可从亲本遗传到
子代细胞通过表观遗传机制。在另一项研究中,我们有
确定的DICE(IL-4承诺的决定因素),一个数量性状基因座
小鼠16号染色体,参与决定最近的
激活了致力于产生IL-4的CD4T细胞。我们推测,
IL-4基因的独立等位基因调节可能是一种
进化的机制赋予它的表达以概率的元素。这
提案有三个目标,由理解
等位基因独立和表观遗传的生物学功能
细胞因子基因表达及其分子机制的研究
在这个过程中。首先,我们将确定反式和顺式基因决定因素
通过解决以下问题实现IL-4基因座的独立等位基因激活
假设:a)给定的IL-4等位基因被激活的概率为
基因决定的。1b)骰子是一个反决定因素
IL-4等位基因激活。2)IL-4等位基因被激活的概率为
受作用于顺式基因的遗传因素的影响。3)等位基因的概率
IL-4基因的激活影响等位基因激活的概率
在邻近的地点。第二,我们将确定以下因素的结构相关性
长期研究IL-4基因座的独立等位基因激活
抗原特异性CD4T细胞克隆以解决以下假设:1)IL-4
等位基因激活与等位基因特异性DNA酶I的出现相关
过敏性部位。2)IL-4等位基因激活与
等位基因特异性去甲基化。最后,我们将解决遗传间隔的问题
小鼠16号染色体,包含大约0.2厘米的骰子,用于产卵
为建立按位置克隆骰子的可行性奠定了基础
功能性救援。
项目成果
期刊论文数量(0)
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{{ truncateString('Mark Bix', 18)}}的其他基金
Genetic Basis For Predisposition To Immune Based Disease
免疫性疾病易感性的遗传基础
- 批准号:
8511228 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
Genetic Basis For Predisposition To Immune Based Disease
免疫性疾病易感性的遗传基础
- 批准号:
8604372 - 财政年份:2013
- 资助金额:
$ 30万 - 项目类别:
ENVIRONMENT AND EPIGENETIC CONTROL OF IMMUNE RESPONSES
免疫反应的环境和表观遗传控制
- 批准号:
6712868 - 财政年份:2003
- 资助金额:
$ 30万 - 项目类别:
ENVIRONMENT AND EPIGENETIC CONTROL OF IMMUNE RESPONSES
免疫反应的环境和表观遗传控制
- 批准号:
6561202 - 财政年份:2003
- 资助金额:
$ 30万 - 项目类别:
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