GENOMIC ANALYSIS OF THE SRC FAMILY OF COREGULATORS IN TISSUE METABOLISM
组织代谢中核心调节因子 SRC 家族的基因组分析
基本信息
- 批准号:7477176
- 负责人:
- 金额:$ 34.96万
- 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:2007-08-01 至 2011-07-31
- 项目状态:已结题
- 来源:
- 关键词:AblationAcuteAnimalsBioinformaticsBiological AssayCaloriesClassConditionDefectDevelopmentElementsEnvironmentEpidemicFamilyFamily memberFatty acid glycerol estersFoodFundingGene ExpressionGene Expression RegulationGene TargetingGenerationsGenesGeneticGenetic TranscriptionGenetically Engineered MouseGenomicsGoalsHepaticHomeostasisIndividualLaboratoriesLeadLiverMYBBP1A geneMetabolicMetabolic PathwayMetabolismMicroarray AnalysisMolecularMorbidity - disease rateMusMuscleObesityObesity associated diseaseOrganOverweightPathway interactionsPhenotypePhysical activityPhysiological ProcessesPhysiologyPlayPromoter RegionsRegulationResearch PersonnelRoleSteroid ReceptorsTamoxifenTechnologyTimeTissuesTranscription Regulatory ProteinTransfectionUnited StatesWeightblood glucose regulationchromatin immunoprecipitationdensitygene functionhormone regulationin vivolipid biosynthesismouse modelpostnatalprogramspromoterresearch studysteroid hormonetranscription factor
项目摘要
Obesity and the diseases associated with this condition are the leading cause of morbidity in the United
States. The increase in the percentage of overweight individuals over the last two decades has made obesity
and associated diseases an epidemic in the United States. Defining the molecular mechanisms regulating
energy storage and utilization will lead to more effective ways of treating and controlling obesity. Over the
last decade, a new class of transcription regulatory proteins, the coregulators has been shown to play a
critical role in the regulation of metabolism. These coactivators exert a higher level of control over
transcription by modulating the activity of a network of transcription factors regulating physiological
processes. The coactivator family being investigated by this PPG is the p160 class of coregulators, the
Steroid Receptor Coactivator family (SRC). Members of this family have been shown to be critical in the
regulation of energy conservation and adipogenesis. Over the last funding period, we have used genetically
engineered mouse models (GEMMs) in combination with high density DMA microarray technology to identify
how the SRCs modulate steroid hormone regulation of gene expression. In the course of this analysis, we
have identified specific genes in the liver whose expression is altered by the ablation of SRC-2/TIF2 and
SRC-1. The metabolic pathways in which these genes function correlate with the observed metabolic
phenotype and define the molecular pathways altered by the ablation of SRC-2/TIF2 and SRC-1. The goal
of this proposal will be to investigate the contribution of hepatic SRC-2/TIF2 and SRC-1 in regulation of
glucose and fat utilization. This proposal will identify the transcriptional network coordinated by these
coactivators in the regulation of hepatic physiology. This will be accomplished by achieving the following
specific aims: 1. The role of hepatic SRC-2/TIF2 and SRC-1 in regulating energy homeostasis will be
investigated. 2. The primary target genes regulated by the SRC-2/TIF2 and SRC-1 genes in the liver will be
defined. 3. The network of transcription factors regulated by SRC-2/TIF2 and SRC-1 will be identified using
bioinformatics and molecular approaches in order to identify transcription factor networks dependent upon
SRC-2/TIF2 and SRC-1. 4. The consequences of double hepatic ablation of SRC-2/TIF2 and SRC-1 in the
regulation of energy and weight homeostasis will be investigated.
肥胖和与此相关的疾病是美国发病的主要原因。
states.在过去的二十年里,超重人群的比例增加,
和相关疾病在美国流行。定义调节的分子机制
能量储存和利用将导致治疗和控制肥胖症的更有效的方法。来
近十年来,一类新的转录调节蛋白,辅调节蛋白已被证明在转录过程中起着重要作用。
在调节新陈代谢中起着关键作用。这些共激活因子对以下物质施加更高水平的控制
通过调节调节生理活性的转录因子网络的活性,
流程. PPG研究的共激活因子家族是p160类共调节因子,
类固醇受体辅激活因子家族(SRC)。这个家庭的成员已经被证明是关键的,
能量守恒和脂肪生成的调节。在上一个资助期内,我们使用了基因技术,
工程小鼠模型(GEMM)结合高密度DMA微阵列技术,
SRCs如何调节类固醇激素对基因表达的调节。在分析过程中,我们
已经确定了肝脏中的特定基因,其表达因SRC-2/TIF 2的消融而改变,
SRC-1这些基因发挥功能的代谢途径与观察到的代谢途径相关。
表型和定义由SRC-2/TIF 2和SRC-1的消融改变的分子途径。目标
这项建议的目的是研究肝脏SRC-2/TIF 2和SRC-1在调节肝脏细胞凋亡中的作用。
葡萄糖和脂肪的利用。这项建议将确定转录网络协调这些
在肝脏生理调节中的辅助激活剂。这将通过实现以下目标来实现
具体目标:1.肝SRC-2/TIF 2和SRC-1在调节能量稳态中的作用将被进一步研究。
研究了2.在肝脏中由SRC-2/TIF 2和SRC-1基因调节的主要靶基因将是
定义了3. SRC-2/TIF 2和SRC-1调控的转录因子网络将使用
生物信息学和分子方法,以确定转录因子网络依赖于
SRC-2/TIF 2和SRC-1。4. SRC-2/TIF 2和SRC-1的双重肝消融术的结果
将研究能量和体重稳态的调节。
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)
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Francesco John DeMayo其他文献
Francesco John DeMayo的其他文献
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{{ truncateString('Francesco John DeMayo', 18)}}的其他基金
PROJECT 4 - The Role of COUP - TFII in Endometrial Biology
项目 4 - COUP - TFII 在子宫内膜生物学中的作用
- 批准号:
7683513 - 财政年份:2009
- 资助金额:
$ 34.96万 - 项目类别:
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