Gonadal expression of FSH receptor
FSH 受体的性腺表达
基本信息
- 批准号:7385127
- 负责人:
- 金额:$ 30.61万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2007
- 资助国家:美国
- 起止时间:2007-04-01 至 2012-03-31
- 项目状态:已结题
- 来源:
- 关键词:5&apos Flanking RegionAreaBindingBiological AssayCellsChromatinChromosomes, Artificial, YeastConserved SequenceDNA-Binding ProteinsDeoxyribonuclease IDistalEndocrineEnhancersEnvironmentFertilityFollicle Stimulating HormoneFollicle Stimulating Hormone ReceptorFunctional RNAGametogenesisGene ExpressionGenesGenetic TranscriptionGenomeGenomicsGonadotropinsHumanHypersensitivityInformation ResourcesInvestigationKnockout MiceMapsModelingMutationNucleic Acid Regulatory SequencesNumbersOvaryProcessPropertyProteinsRattusRegulationRegulatory ElementReproductive HealthReproductive systemResearchRoleSiteTestingTestisTissuesTranscriptional RegulationTransfectionTransgenic MiceTransgenic Organismschromatin immunoprecipitationcomparativegonad functiongranulosa cellhomologous recombinationin vivopromoterreceptorresponsesertoli celltranscription factor
项目摘要
DESCRIPTION (provided by applicant): Fshr is a critical component of the endocrine axis that controls gonad function, gametogenesis, and fertility. Characterization of the mechanisms regulating Fshr transcription provides the opportunity to reveal proteins involved in selective gene expression in Sertoli and granulosa cells and expand our understanding of factors regulating reproductive health. To date, transcriptional studies of Fshr have focused only on promoter and 5' flanking sequences. While these analyses are critical to our understanding of Fshr, it appears that regulatory sequences outside this region are important for Fshr transcriptional regulation. Fortunately, our ability to identify such regulatory sequences has advanced significantly due to the extensive progress in genome research, which provides a wealth of new information and resources. The proposed studies combine computation analysis, transcriptional assays, and transgenic approaches to further our understanding of the processes controlling Fshr transcription. In Aim I, studies are proposed to use mouse knockout models and chromatin immunoprecipitation to evaluate the in vivo roles of transcription factors implicated in Fshr regulation and expand our understanding of the mechanisms regulating transcription through the proximal promoter. In Aim II, comparative genomics, DNase I hypersensitivity mapping and transient transfection analysis will be used to identify distal regulatory regions within the Fshr locus. DNA/protein binding studies will be used to identify proteins associated with important regulatory elements. Aim III proposes to use transgenic mice for in vivo characterization of Fshr regulatory elements. An Fshr-containing yeast artificial chromosome (YAC) will be used to generate transgenic mice that will be characterized for expression in various tissues. Mutations within proposed regulatory elements will be generated in the YAC by homologous recombination and tested for correct expression in transgenic mice, to evaluate their role in vivo. The proposed studies will reveal regulatory elements and proteins needed for Fshr expression, leading not only to a better understanding of its transcriptional control but to the basic principles governing gonadal function, fertility, and generalized gene transcription. By advancing our understanding in these areas, we enhance our ability to evaluate matters of human reproductive health and to develop strategies to assist fertility problems and management.
描述(由申请方提供):Fshr是控制性腺功能、配子发生和生育力的内分泌轴的关键组分。FSHR转录调节机制的表征提供了一个机会,揭示支持细胞和颗粒细胞中参与选择性基因表达的蛋白质,并扩大我们对调节生殖健康因素的理解。迄今为止,Fshr的转录研究仅集中在启动子和5'侧翼序列。虽然这些分析对我们理解FSHR至关重要,但似乎该区域外的调控序列对FSHR转录调控很重要。幸运的是,由于基因组研究的广泛进展,我们识别这种调控序列的能力已经显着提高,这提供了丰富的新信息和资源。拟议的研究结合联合收割机计算分析,转录测定和转基因的方法,以进一步了解控制FSHR转录的过程。在目的一,研究提出使用小鼠基因敲除模型和染色质免疫沉淀,以评估在体内的作用,转录因子参与FSHR的调控,并扩大我们的理解,通过近端启动子调控转录的机制。在目标II中,比较基因组学,DNase I超敏反应作图和瞬时转染分析将用于确定FSHR基因座内的远端调控区。DNA/蛋白质结合研究将用于鉴定与重要调控元件相关的蛋白质。目的III建议使用转基因小鼠在体内表征FSHR调控元件。含有Fshr的酵母人工染色体(YAC)将用于产生转基因小鼠,这些小鼠将被表征为在各种组织中表达。通过同源重组在YAC中产生拟定调控元件内的突变,并测试其在转基因小鼠中的正确表达,以评价其体内作用。拟议的研究将揭示FSHR表达所需的调控元件和蛋白质,不仅可以更好地了解其转录控制,而且可以更好地了解性腺功能,生育力和广义基因转录的基本原则。通过增进我们对这些领域的了解,我们提高了评估人类生殖健康问题和制定战略以协助生育问题和管理的能力。
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)
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LESLIE L. HECKERT其他文献
LESLIE L. HECKERT的其他文献
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{{ truncateString('LESLIE L. HECKERT', 18)}}的其他基金
Small Molecule Inhibitors of DMRT1-Regulated Target Genes as Male Contraceptives
DMRT1 调控靶基因的小分子抑制剂作为男性避孕药
- 批准号:
8066370 - 财政年份:2010
- 资助金额:
$ 30.61万 - 项目类别:
Hormonal and cell-specific regulation of Dmrt1
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6905540 - 财政年份:2002
- 资助金额:
$ 30.61万 - 项目类别:
Hormonal and cell-specific regulation of Dmrt1
Dmrt1 的激素和细胞特异性调节
- 批准号:
7093150 - 财政年份:2002
- 资助金额:
$ 30.61万 - 项目类别:
Hormonal and cell-specific regulation of Dmrt1
Dmrt1 的激素和细胞特异性调节
- 批准号:
6765242 - 财政年份:2002
- 资助金额:
$ 30.61万 - 项目类别:
Hormonal and cell-specific regulation of Dmrt1
Dmrt1 的激素和细胞特异性调节
- 批准号:
6473084 - 财政年份:2002
- 资助金额:
$ 30.61万 - 项目类别:
Hormonal and cell-specific regulation of Dmrt1
Dmrt1 的激素和细胞特异性调节
- 批准号:
6624218 - 财政年份:2002
- 资助金额:
$ 30.61万 - 项目类别:
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