FUNCTIONAL CHARACTERIZATION OF THE PRDM10-ZN FINGER TRANSCRIPTION FACTOR IN EARLY MAMMALIAN DEVELOPMENT
PRDM10-ZN 指转录因子在早期哺乳动物发育中的功能特征
基本信息
- 批准号:10477941
- 负责人:
- 金额:$ 36.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2021
- 资助国家:美国
- 起止时间:2021-08-31 至 2026-04-30
- 项目状态:未结题
- 来源:
- 关键词:AT Rich SequenceAddressAdultAgingApoptosisAutomobile DrivingBindingBiological ModelsCatalytic DomainCell Cycle ProgressionCell physiologyCellsChromatinChromatin StructureCommunicationComplexCouplesCuesDNADNA BindingDNA Binding DomainDataDefectDeveloped CountriesDevelopmentDevelopmental ProcessDiagnosisDiseaseDropsEmbryoEmbryonic DevelopmentEventFamilyFamily PlanningFamily memberFertilityFingersFutureGene ActivationGene ExpressionGenesGeneticGenetic TranscriptionGerm CellsGlutamineHerpes zoster diseaseInfertilityKnowledgeLinkLysineMalignant Fibrous HistiocytomaMethyltransferaseMitoticModelingMusNatureOncogenicOocytesOogenesisPathologicPathway interactionsPatientsPharmacologyPhenotypePre-implantation Embryo DevelopmentPregnancy ComplicationsProcessPropertyProteinsRegulationReproductive BiologyReproductive MedicineResearchRoleSET DomainScienceSignal TransductionSocietiesSoft tissue sarcomaTimeTissuesTranscription CoactivatorTranscriptional ActivationTranscriptional RegulationTranslational RegulationTranslationsVertebratesWorkbaseembryonic stem cellepigenetic regulationexperimental studyextracellulargene networkidiopathic infertilityinhibitormemberparalogous geneprogramspromoterprotein expressionside effectstem cell biologytranscription factorzygote
项目摘要
SUMMARY
During embryonic development and lineage specification, a complex set of extracellular signals is integrated
on chromatin by Master Transcription Factors (TF) that modify chromatin structure and gene expression. PRDM
proteins are TFs, containing a PR-methyltransferase domain at their N-terminus and DNA-binding Zn-fingers at
their C-terminus. All 17 PRDM family members are well known for their role as master regulator of lineage
specification and their deregulated expression is often linked to diseases.
Our group has characterized the function of PRDM10, a transcriptional activator, orchestrating mouse
preimplantation development. Our preliminary data indicate that: 1) Prdm10 zygotic KO embryos have visible
defects at embryonic day E3.5; 2) Prdm10 maternal (Zona Pellucida3 (Zp3)-CRE) KO embryos arrest at the
zygote/two-cell stage; 3) PRDM10 is unique among PRDM family members, as it contains a Glutamine-rich
coactivator domain at its C-terminus. Based on this preliminary data we propose the following experiments:
In Aim1 we will determine the function of maternal PRDM10. We will take advantage of the Zp3-CRE
strain, to delete Prdm10 in the oocyte, and deplete the PRDM10 maternal protein contribution in the zygote. This
will allow us to study the function of PRDM10 before zygotic transcriptional activation and determine the gene
network directly regulated by PRDM10.
In Aim2 we will determine the mechanism of action of PRDM10 as a transcription factor. In this aim we
will characterize the mode of action of PRDM10 (i.e. its methyltransferase activity, its protein interactome, and
its transcriptional activation and DNA binding-properties). We will also specifically address PRDM10’s function
in dictating the choice of alternative promoter usage. Finally, we will validate the function in oocyte and early
embryogenesis of key PRDM10-downstream effectors.
The significance of these studies is that Prdm10 is an uncharacterized maternal effect gene, and knowledge
of the pathways regulated by this Zn-finger TF will be useful to the field of stem cell biology and reproductive
medicine.
总结
在胚胎发育和谱系特化过程中,一组复杂的细胞外信号被整合
主转录因子(TF)修饰染色质结构和基因表达。PRDM
蛋白质是TF,在其N末端含有PR-甲基转移酶结构域,在其N末端含有DNA结合锌指,
他们的C末端PRDM家族的所有17名成员都因其作为血统主要调节者的角色而闻名
基因特化及其失调表达通常与疾病有关。
我们的小组已经表征了PRDM 10的功能,PRDM 10是一种转录激活因子,
着床前发育我们的初步数据表明:1)Prdm 10合子KO胚胎具有可见的
2)Prdm 10母体(透明带3(Zp 3)-CRE)KO胚胎在E3.5天停滞,
3)PRDM 10在PRDM家族成员中是独特的,因为它含有富含谷氨酰胺的蛋白质。
在其C-末端的辅激活因子结构域。基于这些初步数据,我们提出以下实验:
在Aim 1中,我们将确定母体PRDM 10的功能。我们将利用Zp 3-CRE
菌株,以删除卵母细胞中的Prdm 10,并耗尽受精卵中的PRDM 10母体蛋白贡献。这
这将使我们能够研究PRDM 10在合子转录激活前的功能,并确定基因
由PRDM 10直接管理的网络。
在Aim 2中,我们将确定PRDM 10作为转录因子的作用机制。为此,我们
将表征PRDM 10的作用模式(即其甲基转移酶活性、其蛋白质相互作用组和其代谢产物)。
其转录激活和DNA结合性质)。我们还将专门讨论PRDM 10的功能
在决定替代启动子使用的选择方面。最后,我们将在卵母细胞和早期验证其功能。
关键PRDM 10下游效应子的胚胎发生。
这些研究的意义在于,Prdm 10是一个未表征的母体效应基因,
这种锌指TF调控的途径将有助于干细胞生物学和生殖领域
药
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 }}
Ernesto Guccione其他文献
Ernesto Guccione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('Ernesto Guccione', 18)}}的其他基金
Implementation of a qPCR-based assay for the quantification of SARS-CoV-2-specific T cells in immunocompromised patients
实施基于 qPCR 的检测方法,对免疫功能低下患者的 SARS-CoV-2 特异性 T 细胞进行定量
- 批准号:
10580531 - 财政年份:2023
- 资助金额:
$ 36.34万 - 项目类别:
FUNCTIONAL CHARACTERIZATION OF NOVEL DETERMINANTS OF HOLOPROSENCEPHALY (HPE)
前脑无裂畸形 (HPE) 的新决定因素的功能特征
- 批准号:
10366059 - 财政年份:2021
- 资助金额:
$ 36.34万 - 项目类别:
Resource Core D - Bioinformatics and Statistical Analysis Core
资源核心 D - 生物信息学和统计分析核心
- 批准号:
10676795 - 财政年份:2021
- 资助金额:
$ 36.34万 - 项目类别:
Resource Core D - Bioinformatics and Statistical Analysis Core
资源核心 D - 生物信息学和统计分析核心
- 批准号:
10463725 - 财政年份:2021
- 资助金额:
$ 36.34万 - 项目类别:
FUNCTIONAL CHARACTERIZATION OF NOVEL DETERMINANTS OF HOLOPROSENCEPHALY (HPE)
前脑无裂畸形 (HPE) 的新决定因素的功能特征
- 批准号:
10596128 - 财政年份:2021
- 资助金额:
$ 36.34万 - 项目类别:
FUNCTIONAL CHARACTERIZATION OF THE PRDM10-ZN FINGER TRANSCRIPTION FACTOR IN EARLY MAMMALIAN DEVELOPMENT
PRDM10-ZN 指转录因子在早期哺乳动物发育中的功能特征
- 批准号:
10617819 - 财政年份:2021
- 资助金额:
$ 36.34万 - 项目类别:
DISSECTING THE ROLE OF PRDM15 IN NORMAL HEMATOPOIESIS AND B-CELL MALIGNANCIES
剖析 PRDM15 在正常造血和 B 细胞恶性肿瘤中的作用
- 批准号:
10316262 - 财政年份:2020
- 资助金额:
$ 36.34万 - 项目类别:
Therapeutic targeting of RNA splicing catalysis through inhibition of Protein Arginine Methylation
通过抑制蛋白质精氨酸甲基化来治疗 RNA 剪接催化
- 批准号:
10165673 - 财政年份:2020
- 资助金额:
$ 36.34万 - 项目类别:
Therapeutic targeting of RNA splicing catalysis through inhibition of Protein Arginine Methylation
通过抑制蛋白质精氨酸甲基化来治疗 RNA 剪接催化
- 批准号:
10703206 - 财政年份:2020
- 资助金额:
$ 36.34万 - 项目类别:
Therapeutic targeting of RNA splicing catalysis through inhibition of Protein Arginine Methylation
通过抑制蛋白质精氨酸甲基化来治疗 RNA 剪接催化
- 批准号:
10393007 - 财政年份:2020
- 资助金额:
$ 36.34万 - 项目类别:
相似海外基金
Rational design of rapidly translatable, highly antigenic and novel recombinant immunogens to address deficiencies of current snakebite treatments
合理设计可快速翻译、高抗原性和新型重组免疫原,以解决当前蛇咬伤治疗的缺陷
- 批准号:
MR/S03398X/2 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Fellowship
Re-thinking drug nanocrystals as highly loaded vectors to address key unmet therapeutic challenges
重新思考药物纳米晶体作为高负载载体以解决关键的未满足的治疗挑战
- 批准号:
EP/Y001486/1 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Research Grant
CAREER: FEAST (Food Ecosystems And circularity for Sustainable Transformation) framework to address Hidden Hunger
职业:FEAST(食品生态系统和可持续转型循环)框架解决隐性饥饿
- 批准号:
2338423 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Continuing Grant
Metrology to address ion suppression in multimodal mass spectrometry imaging with application in oncology
计量学解决多模态质谱成像中的离子抑制问题及其在肿瘤学中的应用
- 批准号:
MR/X03657X/1 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Fellowship
CRII: SHF: A Novel Address Translation Architecture for Virtualized Clouds
CRII:SHF:一种用于虚拟化云的新型地址转换架构
- 批准号:
2348066 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Standard Grant
BIORETS: Convergence Research Experiences for Teachers in Synthetic and Systems Biology to Address Challenges in Food, Health, Energy, and Environment
BIORETS:合成和系统生物学教师的融合研究经验,以应对食品、健康、能源和环境方面的挑战
- 批准号:
2341402 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Standard Grant
The Abundance Project: Enhancing Cultural & Green Inclusion in Social Prescribing in Southwest London to Address Ethnic Inequalities in Mental Health
丰富项目:增强文化
- 批准号:
AH/Z505481/1 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Research Grant
ERAMET - Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
ERAMET - 快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10107647 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
EU-Funded
Ecosystem for rapid adoption of modelling and simulation METhods to address regulatory needs in the development of orphan and paediatric medicines
快速采用建模和模拟方法的生态系统,以满足孤儿药和儿科药物开发中的监管需求
- 批准号:
10106221 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
EU-Funded
Recite: Building Research by Communities to Address Inequities through Expression
背诵:社区开展研究,通过表达解决不平等问题
- 批准号:
AH/Z505341/1 - 财政年份:2024
- 资助金额:
$ 36.34万 - 项目类别:
Research Grant