Maternal transcription factors shaping early embryonic chromatin landscape
母体转录因子塑造早期胚胎染色质景观
基本信息
- 批准号:10570971
- 负责人:
- 金额:$ 41.05万
- 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:2021-03-01 至 2026-02-28
- 项目状态:未结题
- 来源:
- 关键词:3-DimensionalAddressArchitectureAreaBindingBiologyCell Differentiation processCell NucleusCellsChIP-seqChromatinCodeComplexDNA SequenceDevelopmentDevelopmental GeneEmbryoEnhancersEnsureEpigenetic ProcessEventFOXH1 geneGene ActivationGene ExpressionGenesGenetic TranscriptionGenomeGenomic approachGerm LayersGoalsModificationNucleosomesPhaseProcessProteinsRanaRegimenRegulator GenesResearchRoleSeriesShapesSiteSystemTimeWorkcell typecombinatorialgenome-widehistone modificationimaging approachin vivoinsightmolecular assembly/self assemblypluripotencyprogramstranscription factortranscriptomezygote
项目摘要
Project Summary:
How the early embryonic genome – through a progressive series of epigenetic modifications controls zygotic
gene transcription, both in `time and space' – to ensure proper cellular differentiation programs, is a major
question in biology. Crucial to this process is the activity of a subset of transcription factors (TFs), which sit
high in the regulatory hierarchy to control gene expression through combinatorial interactions with cis-
regulatory modules (CRMs) that include enhancers, insulators and silencers. DNA sequence motifs present in
the CRMs of genes act as a code to dictate which genes are to be utilized at the right time, and thus activate
specific gene regulatory programs. ChIP-seq analysis of many TFs usually identifies tens of thousands of TF
binding “peaks,” genomewide, for a given cell type, but only a fraction of these sites appears to be functional. If
so, what mechanistic constrains are needed to properly regulate gene expression? These questions are
fundamentally important, but a difficult question to address in vivo using mammalian embryos due to the need
for relatively large numbers of embryos for genome-scale analyses across numerous experimental regimens.
Here we tackle this question by leveraging the strengths of the frog embryo system and examine the events of
zygotic genome activation (ZGA). As the embryo transitions from fertilized egg to pluripotent zygotic cells
giving rise to three germ layer cell fates, the embryonic genome and transcriptome need to be rapidly
reprogrammed. How can maternal TFs collectively reprogram the genome during the ZGA remains an
important area for the current research. Our recent work shows that a network of maternal TFs encoding Fox,
Sox and Pou type proteins acts through conserved mechanisms to reprogram the cellular genome into the
embryonic states. This is in part accomplished by forming enhanceososme complexes on the enhancers of
target genes, resulting in changing in histone modifications surrounding genes, and forming super enhances,
which concentrate the transcription apparatus and form phase-separated multimolecular assemblies in the
nucleus. Our premise is that maternally expressed Foxh1 and its interacting partner TFs (Sox3 and
Pou5f) function at the top of a hierarchy of TF interactions to not only mark developmental genes for
activation prior to the onset of zygotic gene expression, but also coordinate major reorganization of
the epigenetic landscape during ZGA. Through our efforts to elucidate these conserved developmental
mechanisms controlling pluripotency, our goal is to uncover the integrative roles of maternal TFs in regulating
the onset of ZGA, coordinating nucleosome phasing and histone modifications on target genes, and shaping
the 3D architecture of chromatin. We combine both genomic and imaging approaches to provide important
insights into the unifying principles that drive genome activation.
1
项目概要:
早期胚胎基因组如何通过一系列渐进的表观遗传修饰控制合子
基因转录,无论是在“时间和空间”-以确保适当的细胞分化程序,是一个主要的
生物学中的问题这一过程的关键是转录因子(TF)的一个子集的活性,这些转录因子位于
在调控层次中处于高位,通过与顺式-
调节模块(CRM)包括增强子、绝缘子和沉默子。DNA序列基序存在于
基因的标准物质作为一种编码,指示哪些基因在正确的时间被利用,从而激活
特定的基因调控程序。许多TF的ChIP-seq分析通常鉴定出数万个TF,
结合“峰”,对于一个给定的细胞类型,但只有一小部分这些网站似乎是功能性的。如果
那么,需要什么样的机制约束来适当地调节基因表达呢?这些问题都是
这是一个非常重要的问题,但由于需要使用哺乳动物胚胎在体内解决这个问题是困难的。
用于在众多实验方案中进行基因组规模分析的相对大量的胚胎。
在这里,我们通过利用青蛙胚胎系统的优势来解决这个问题,并检查
合子基因组激活(ZGA)。当胚胎从受精卵转变为多能合子细胞时
胚胎基因组和转录组需要迅速地
重新编程在ZGA期间,母体TF如何共同重新编程基因组仍然是一个问题。
是当前研究的重要领域。我们最近的工作表明,编码Fox的母体TF网络,
Sox和Pou型蛋白通过保守的机制将细胞基因组重编程为
胚胎状态这部分是通过在增强子上形成增强体复合物来实现的。
靶基因,导致改变基因周围的组蛋白修饰,并形成超级增强,
其集中转录装置并在细胞中形成相分离的多分子组装体,
原子核我们的前提是,母系表达的Foxh 1及其相互作用伙伴TF(Sox 3和Sox 4),
Pou 5 f)在TF相互作用的层次结构的顶部起作用,不仅标记发育基因,
在合子基因表达开始之前激活,而且还协调
ZGA期间的表观遗传景观。通过我们的努力来阐明这些保守的发展
控制多能性的机制,我们的目标是揭示母体TF在调节多能性中的整合作用。
ZGA的开始,协调靶基因上的核小体定相和组蛋白修饰,以及
染色质的三维结构。我们联合收割机结合基因组和成像方法,
深入了解驱动基因组激活的统一原则。
1
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 }}
Ken W.Y. Cho其他文献
Maternal and zygotic contributions to H3K4me1 chromatin marking during germ layer formation
- DOI:
10.1016/j.ydbio.2024.11.006 - 发表时间:
2025-02-01 - 期刊:
- 影响因子:
- 作者:
Kitt D. Paraiso;Ira L. Blitz;Ken W.Y. Cho - 通讯作者:
Ken W.Y. Cho
Uncovering the roles of BMP signaling during mouse embryogenesis
- DOI:
10.1016/j.ydbio.2009.05.363 - 发表时间:
2009-07-15 - 期刊:
- 影响因子:
- 作者:
Anna L. Javier;Linda Doan;Ira Blitz;Edwin Monuki;Ken W.Y. Cho - 通讯作者:
Ken W.Y. Cho
FoxH1 function in target gene selection and in transcriptional noise control
- DOI:
10.1016/j.ydbio.2011.05.519 - 发表时间:
2011-08-01 - 期刊:
- 影响因子:
- 作者:
William Chiu;Ira Blitz;Rebekah Charney;Jin Cho;Eddie Park;Mike Gilchrist;Ken W.Y. Cho - 通讯作者:
Ken W.Y. Cho
Ken W.Y. Cho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('Ken W.Y. Cho', 18)}}的其他基金
Spatiotemporal mapping of enhancer activity in developing frog embryos
青蛙胚胎发育中增强子活性的时空图谱
- 批准号:
10511083 - 财政年份:2022
- 资助金额:
$ 41.05万 - 项目类别:
Spatiotemporal mapping of enhancer activity in developing frog embryos
青蛙胚胎发育中增强子活性的时空图谱
- 批准号:
10686937 - 财政年份:2022
- 资助金额:
$ 41.05万 - 项目类别:
Maternal transcription factors shaping early embryonic chromatin landscape
母体转录因子塑造早期胚胎染色质景观
- 批准号:
10353368 - 财政年份:2021
- 资助金额:
$ 41.05万 - 项目类别:
Maternal transcription factors shaping early embryonic chromatin landscape
母体转录因子塑造早期胚胎染色质景观
- 批准号:
10389644 - 财政年份:2021
- 资助金额:
$ 41.05万 - 项目类别:
Assessment of the phasor Fluorescence Lifetime Imaging Microscopy (FLIM) Approach in an animal model
相量荧光寿命成像显微镜 (FLIM) 方法在动物模型中的评估
- 批准号:
9396700 - 财政年份:2017
- 资助金额:
$ 41.05万 - 项目类别:
Deciphering the gene regulatory network controlling vertebrate endodermal fates
破译控制脊椎动物内胚层命运的基因调控网络
- 批准号:
9256494 - 财政年份:2013
- 资助金额:
$ 41.05万 - 项目类别:
Deciphering the gene regulatory network controlling vertebrate endodermal fates
破译控制脊椎动物内胚层命运的基因调控网络
- 批准号:
8858659 - 财政年份:2013
- 资助金额:
$ 41.05万 - 项目类别:
Deciphering the gene regulatory network controlling vertebrate endodermal fates
破译控制脊椎动物内胚层命运的基因调控网络
- 批准号:
8692986 - 财政年份:2013
- 资助金额:
$ 41.05万 - 项目类别:
Deciphering the gene regulatory network controlling vertebrate endodermal fates
破译控制脊椎动物内胚层命运的基因调控网络
- 批准号:
9054884 - 财政年份:2013
- 资助金额:
$ 41.05万 - 项目类别:
Deciphering the gene regulatory network controlling vertebrate endodermal fates
破译控制脊椎动物内胚层命运的基因调控网络
- 批准号:
8561007 - 财政年份:2013
- 资助金额:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 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:
$ 41.05万 - 项目类别:
Research Grant