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

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)

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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

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{{ 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:

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