Mechanism of Chromatin Insulator Imprinting
染色质绝缘体印迹机制
基本信息
- 批准号:6852647
- 负责人:
- 金额:$ 36.75万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2002
- 资助国家:美国
- 起止时间:2002-04-01 至 2007-03-31
- 项目状态:已结题
- 来源:
- 关键词:DNA binding proteinDNA footprintingDNA methylationPrader Willi syndromeallelesbinding siteschromatinchromosomesdevelopmental geneticsflow cytometrygel mobility shift assaygene expressiongenetic mappinggenetic regulatory elementgenetically modified animalsgenomic imprintinggerm cellshydatidiform moleinsulinlike growth factorlaboratory mousenucleic acid sequencepolymerase chain reactionprotein bindingsite directed mutagenesisteratoma
项目摘要
DESCRIPTION (provided by applicant): The broad long term objective is to
determine the mechanism and role in development of the epigenetic -system of
genomic imprinting. Imprinting of the H19 and insulin-like growth factor 2
(Igf2) genes (resulting in their monoallelic expression) is achieved through
paternal-specific methylation of a 2.4 kb imprinting control region (ICR) as
inherited from the male germ line. The specific aims are designed to further
understanding of (1) how male germ cell-specific methylation of the ICR is
achieved-this would be the imprinting mechanism, and (2) how the maternal ICR
functions as a chromatin insulator in somatic cells. The specific aims are (1)
in somatic cells, to map the ICR for sites of parent-of-origin allele-specific
protein binding, and similarly, in germ cells, to map the ICR for sites of
sex-specific protein binding. Sites characterized in this way will be
candidates for mediating imprinting or male germ cell-specific ICR methylation.
(2) Mutate these candidate sites in mice to test their role in mediating
imprinting, and (3) identify the proteins binding to these sites. The
hypothesis being tested by these aims is that there is a "primary protein
difference" between the two germ lines which determines imprinting. These
studies are related to health in that genomic imprinting underlies a number of
human diseases, e.g., hydatidiform mole, ovarian teratoma, and the Prader-Willi
and Beckwith-Wiedemann syndromes. Further understanding of the genetic basis of
genomic imprinting will therefore shed light on the genetic basis of these
diseases. The research design and methods for achieving this goal will involve
(1) in vivo footprinting of the ICR to visualize protein binding sites, (2)
targeted mutagenesis of ICR sites in mice and assessment of effects on
imprinting by allele-specific expression and methylation analysis of H19 and
Igf2, and (3) competitive and supershift electrophoretic mobility shift assays
to identify proteins binding to ICR sites. Further assessment of protein
identity by examining mouse mutants for candidate proteins.
描述(由申请人提供):广泛的长期目标是
项目成果
期刊论文数量(0)
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Piroska Edit Szabó其他文献
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{{ truncateString('Piroska Edit Szabó', 18)}}的其他基金
A NOVEL PROCESS SAFEGUARDS GENOME INTEGRITY IN THE MAMMALIAN GERM LINE
保护哺乳动物生殖系基因组完整性的新工艺
- 批准号:
10445720 - 财政年份:2022
- 资助金额:
$ 36.75万 - 项目类别:
A Novel Process Safeguards Genome Integrity In The Mammalian Germ Line-Administrative Supplement to Support Undergraduate Summer Research Experiences
一种保护哺乳动物种系基因组完整性的新方法——支持本科生暑期研究经历的行政补充
- 批准号:
10807301 - 财政年份:2022
- 资助金额:
$ 36.75万 - 项目类别:
A NOVEL PROCESS SAFEGUARDS GENOME INTEGRITY IN THE MAMMALIAN GERM LINE
保护哺乳动物生殖系基因组完整性的新工艺
- 批准号:
10650391 - 财政年份:2022
- 资助金额:
$ 36.75万 - 项目类别:
Epigenetic effects if endocrine disruptors in fetal germ cells
胎儿生殖细胞中内分泌干扰物的表观遗传效应
- 批准号:
7645030 - 财政年份:2006
- 资助金额:
$ 36.75万 - 项目类别:
Epigenetic effects if endocrine disruptors in fetal germ cells
胎儿生殖细胞中内分泌干扰物的表观遗传效应
- 批准号:
7289321 - 财政年份:2006
- 资助金额:
$ 36.75万 - 项目类别:
Epigenetic effects if endocrine disruptors in fetal germ cells
胎儿生殖细胞中内分泌干扰物的表观遗传效应
- 批准号:
7448600 - 财政年份:2006
- 资助金额:
$ 36.75万 - 项目类别:
Epigenetic effects if endocrine disruptors in fetal germ cells
胎儿生殖细胞中内分泌干扰物的表观遗传效应
- 批准号:
7171695 - 财政年份:2006
- 资助金额:
$ 36.75万 - 项目类别:
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