Developmental gene poising by Oct transcription factors
Oct 转录因子的发育基因平衡
基本信息
- 批准号:9896839
- 负责人:
- 金额:$ 30.5万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2018
- 资助国家:美国
- 起止时间:2018-04-01 至 2022-03-31
- 项目状态:已结题
- 来源:
- 关键词:Binding ProteinsBiological ProcessBloodCell Differentiation processCell physiologyCellsChromatin Remodeling FactorCollaborationsDataDefectDevelopmentDevelopmental GeneEnzymesFamily memberGene ActivationGene ExpressionGene Expression RegulationGenerationsGenesGenetic TranscriptionGenomic approachHistonesImmune responseIn VitroLysineMediatingMethylationModelingMolecularNuRD complexOxidative StressProcessProteinsPublishingRegulator GenesRepressionSiteSolidTestingUndifferentiatedWorkblastocystcofactorembryonic stem cellgenetic approachgenome-widein vivoinduced pluripotent stem cellparalogous genepluripotencyrecruitstem cell differentiationstem cellstranscription factor
项目摘要
PROJECT SUMMARY:
Oct4 is a master transcriptional regulator of pluripotency. Intriguingly, embryonic stem cells (ESCs) and
induced pluripotent stem cells (iPSCs) co-express Oct4 together with two paralogs, Oct1 and Oct6. These
proteins bind the same sequences in vitro and many of the same genes in vivo. Their functions in pre-
implantation embryos and ESCs, and immediately following differentiation, are unknown. Though critical early
developmental fate decisions are made as ESCs first lose pluripotency and Oct4 is lost, how this process
works at a molecular level remains a black box. For example, developmentally poised Oct4 targets can be
induced many days after loss of Oct4 itself, raising the question of how poising is maintained. This proposal
focuses on Oct1/Oct6/Oct4 collaboration in pluripotent cells and early during differentiation. We previously
showed that Oct1 either represses gene transcription, by associating with NuRD, or maintains silent genes in a
configuration that allows for later expression, by associating with Jmjd1a/KDM3A to decrease local histone
H3K9 methylation. More recently we showed that Oct1 is dispensable in undifferentiated ESCs, but following
differentiation is required both to induce developmental-specific genes, and to suppress genes specific for
alternative developmental lineages. As a consequence, Oct1 deficient ESCs appear normal but show severe
defects upon differentiation. Oct1 does not occupy these targets in ESCs, presumably due to competition from
the more abundant Oct4 protein. Instead, Oct1 occupies these genes as ESCs differentiate and Oct4 is lost.
We propose a “handoff” model whereby silent but poised genes are occupied by Oct1, and possibly Oct6, to
maintain proper developmental gene expression. We will test this model by identifying common and unique
Oct1/Oct4/Oct6 target sites genome-wide in differentiating ESCs, determining whether handoff of cofactors
accompanies Oct4 replacement by Oct1 in differentiating cells, and studying Oct1-mediated repression of
lineage-inappropriate genes, which are ectopically expressed upon differentiation of Oct1 deficient ESCs.
Aim 1: Test the validity of the handoff model.
Aim 2: Define the cofactors used by Oct1 and Oct4 at developmentally inducible targets in pluripotent cells and
immediately after differentiation.
Aim 3: Determine the mechanism by which Oct1 represses lineage-inappropriate genes.
项目总结:
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 }}
DEAN TANTIN其他文献
DEAN TANTIN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('DEAN TANTIN', 18)}}的其他基金
Role of transcription coactivator OCA-B in gene poising and immunological memory.
转录辅激活因子 OCA-B 在基因平衡和免疫记忆中的作用。
- 批准号:
8457551 - 财政年份:2012
- 资助金额:
$ 30.5万 - 项目类别:
Role of Transcription Coactivator OCA-B in Gene Poising and Immunological Memory
转录辅激活因子 OCA-B 在基因平衡和免疫记忆中的作用
- 批准号:
10324572 - 财政年份:2012
- 资助金额:
$ 30.5万 - 项目类别:
Role of transcription coactivator OCA-B in gene poising and immunological memory.
转录辅激活因子 OCA-B 在基因平衡和免疫记忆中的作用。
- 批准号:
8585815 - 财政年份:2012
- 资助金额:
$ 30.5万 - 项目类别:
Role of Oct Transcription Factors Regulating Immune Response
Oct 转录因子调节免疫反应的作用
- 批准号:
8437617 - 财政年份:2012
- 资助金额:
$ 30.5万 - 项目类别:
Role of Transcription Coactivator OCA-B in Gene Poising and Immunological Memory
转录辅激活因子 OCA-B 在基因平衡和免疫记忆中的作用
- 批准号:
10084248 - 财政年份:2012
- 资助金额:
$ 30.5万 - 项目类别:
Gene regulation of Oct1: implications of metabolism, stemness and cancer
Oct1 的基因调控:代谢、干性和癌症的影响
- 批准号:
8022880 - 财政年份:2010
- 资助金额:
$ 30.5万 - 项目类别:
Gene regulation of Oct1: implications of metabolism, stemness and cancer
Oct1 的基因调控:代谢、干性和癌症的影响
- 批准号:
7881146 - 财政年份:2010
- 资助金额:
$ 30.5万 - 项目类别:
相似海外基金
Nitrous Oxide Management in a Novel Biological Process
新型生物过程中的一氧化二氮管理
- 批准号:
2789227 - 财政年份:2023
- 资助金额:
$ 30.5万 - 项目类别:
Studentship
Dynamic regulation of RNA modification and biological process
RNA修饰和生物过程的动态调控
- 批准号:
18H05272 - 财政年份:2018
- 资助金额:
$ 30.5万 - 项目类别:
Grant-in-Aid for Scientific Research (S)
Micro-Scale Biological Process Automation: Modelling, Sensing and Control
微尺度生物过程自动化:建模、传感和控制
- 批准号:
42116-2013 - 财政年份:2017
- 资助金额:
$ 30.5万 - 项目类别:
Discovery Grants Program - Individual
Micro-Scale Biological Process Automation: Modelling, Sensing and Control
微尺度生物过程自动化:建模、传感和控制
- 批准号:
42116-2013 - 财政年份:2016
- 资助金额:
$ 30.5万 - 项目类别:
Discovery Grants Program - Individual
Organizing the Waterloo Biofilter biological process for treating wastewater concentrated by extreme water conservation plumbing
组织滑铁卢生物过滤器生物工艺处理通过极端节水管道浓缩的废水
- 批准号:
479764-2015 - 财政年份:2015
- 资助金额:
$ 30.5万 - 项目类别:
Engage Grants Program
Micro-Scale Biological Process Automation: Modelling, Sensing and Control
微尺度生物过程自动化:建模、传感和控制
- 批准号:
42116-2013 - 财政年份:2015
- 资助金额:
$ 30.5万 - 项目类别:
Discovery Grants Program - Individual
Development of Biological Process for VOC treatment
VOC处理生物工艺的开发
- 批准号:
476672-2014 - 财政年份:2015
- 资助金额:
$ 30.5万 - 项目类别:
Experience Awards (previously Industrial Undergraduate Student Research Awards)
Micro-Scale Biological Process Automation: Modelling, Sensing and Control
微尺度生物过程自动化:建模、传感和控制
- 批准号:
42116-2013 - 财政年份:2014
- 资助金额:
$ 30.5万 - 项目类别:
Discovery Grants Program - Individual
Optimization of a biological process treating winery wastewater: anaerobic digestion integrated with Waterloo biofilter
处理酿酒厂废水的生物工艺优化:厌氧消化与滑铁卢生物过滤器集成
- 批准号:
463193-2014 - 财政年份:2014
- 资助金额:
$ 30.5万 - 项目类别:
Engage Grants Program
Micro-Scale Biological Process Automation: Modelling, Sensing and Control
微尺度生物过程自动化:建模、传感和控制
- 批准号:
42116-2013 - 财政年份:2013
- 资助金额:
$ 30.5万 - 项目类别:
Discovery Grants Program - Individual