Regulation and function of H2A.Z during the mid-blastula transition

H2A.Z 在囊胚中期转变过程中的调节和功能

基本信息

  • 批准号:
    10659012
  • 负责人:
  • 金额:
    $ 33.11万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2022
  • 资助国家:
    美国
  • 起止时间:
    2022-07-04 至 2027-03-31
  • 项目状态:
    未结题

项目摘要

PROJECT SUMMARY Developmental progression from cleavage phase to gastrulation occurs during the mid-blastula transition (MBT). This transition coincides with several critical events, including maternal to zygotic transition, zygotic genome activation (ZGA), and stem cell formation. How the zygotic genome becomes activate and how proper developmental timing is regulated are critical unknowns in biology. Recent data in zebrafish and Drosophila indicate that these processes are highly sensitive to the levels a particular histone, the histone variant H2A.Z (H2Av in Drosophila). However, it remains largely unknown why altered H2A.Z levels disrupt MBT events and how the embryo ordinarily assures that the correct amount of H2A.Z is incorporated into chromatin. Preliminary observations indicate that in both species a subset of zygotic genes is prematurely activated when H2A.Z levels are elevated. A combination of genomics approaches and expression analysis of candidate genes will be used to determine the temporal pattern of gene activation in embryos with up- or downregulated nuclear H2A.Z levels. It will also be tested to what extent the observed changes are due to chromatin associated factors (in particular the pattern of H2A.Z distribution across the genome) and epigenetic marks. Use of the two distinct model systems will reveal to what extent the underlying mechanisms are conserved between vertebrates and insects. In Drosophila, it is known that H2A.Z levels in the nucleus can be regulated by the H2A.Z binding protein Jabba that sequesters H2A.Z in the cytoplasm, a process active during the time of the MBT. Preliminary studies have led to the hypothesis that a different H2A.Z-binding protein plays an analogous role in zebrafish. This hypothesis will be tested using live imaging, embryo injections, and structure-function analysis. Successful completion of this project will define the role of H2A.Z in controlling gene expression patterns and in cellular programming during one of the most crucial periods of development, the mid- blastula transition.
项目总结 从卵裂期到原肠胚的发育过程发生在囊胚中期 过渡(MBT)。这一转变与几个关键事件不谋而合,包括母体到 合子转化、合子基因组激活(ZGA)和干细胞形成。受精卵是如何 基因组被激活以及如何调节适当的发育时间是至关重要的 生物学中的未知数。斑马鱼和果蝇的最新数据表明,这些过程是 对特定组蛋白的水平高度敏感,组蛋白变异体H_2A.Z(H_2Av在 果蝇)。然而,在很大程度上仍不清楚为什么H_2A.Z水平改变会扰乱MBT事件 以及胚胎通常如何确保正确数量的H2A.Z被掺入 染色质。初步观察表明,在这两个物种中,合子基因的一个子集是 当H_2A.Z水平升高时过早激活。基因组学方法的组合 候选基因的表达分析将被用来确定 核过氧化氢酶水平上调或下调的胚胎中的基因激活。它还将接受测试 观察到的变化在多大程度上是由染色质相关因素(特别是 H_2A.Z在基因组中的分布模式)和表观遗传标记。使用这两个不同的 模型系统将揭示潜在机制在多大程度上是保守的 脊椎动物和昆虫。在果蝇中,已知细胞核中的H2A.Z水平可以是 受H2A.Z结合蛋白Jabba的调节,Jabba将H2A.Z隔离在细胞质中,a 在MBT期间处于活动状态的进程。初步研究导致了一种假设,即 不同的H2A.Z结合蛋白在斑马鱼中起着类似的作用。这一假设将是 使用实时成像、胚胎注射和结构-功能分析进行测试。成功 该项目的完成将确定H2A.Z在控制基因表达模式中的作用 而在最关键的发育时期之一的细胞编程中, 胚泡过渡。

项目成果

期刊论文数量(0)
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Patrick J. Murphy其他文献

Exploring non-participation in colorectal cancer screening: A systematic review of qualitative studies
探索未参与结直肠癌筛查的情况:定性研究的系统综述
  • DOI:
    10.1016/j.socscimed.2023.116022
  • 发表时间:
    2023-07-01
  • 期刊:
  • 影响因子:
    5.000
  • 作者:
    Alice Le Bonniec;Oonagh Meade;Milou Fredrix;Eimear Morrissey;Ronan E. O'Carroll;Patrick J. Murphy;Andrew W. Murphy;Jenny Mc Sharry
  • 通讯作者:
    Jenny Mc Sharry
Xenobiotic metabolism: a look from the past to the future.
异生物质代谢:从过去到未来的展望。
Metabolism of <em>β</em>-Phenethylbiguanide
  • DOI:
    10.1002/jps.2600570707
  • 发表时间:
    1968-07-01
  • 期刊:
  • 影响因子:
  • 作者:
    Patrick J. Murphy;Arne N. Wick
  • 通讯作者:
    Arne N. Wick
Self sensitized photooxidation of tetrathienyltetrathiafulvalenes: synthesis of thienyl substituted 1,2,5,8-tetrathiecine-6,7-dione, a new heterocyclic system
  • DOI:
    10.1016/j.tetlet.2012.12.080
  • 发表时间:
    2013-03-06
  • 期刊:
  • 影响因子:
  • 作者:
    Adam Charlton;Donato Donati;Stefania Fusi;Patrick J. Murphy;Fabio Ponticelli
  • 通讯作者:
    Fabio Ponticelli
Oxidative stress underlies heritable impacts of paternal cigarette smoke exposure
氧化应激是父亲吸烟暴露的遗传影响的基础
  • DOI:
    10.1101/750638
  • 发表时间:
    2019
  • 期刊:
  • 影响因子:
    0
  • 作者:
    Patrick J. Murphy;Jingtao Guo;Timothy G. Jenkins;E. James;J. Hoidal;T. Huecksteadt;Dallin S Broberg;J. Hotaling;David F Alonso;D. Carrell;B. Cairns;K. Aston
  • 通讯作者:
    K. Aston

Patrick J. Murphy的其他文献

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{{ truncateString('Patrick J. Murphy', 18)}}的其他基金

Regulation and function of H2A.Z during the mid-blastula transition
H2A.Z 在囊胚中期转变过程中的调节和功能
  • 批准号:
    10362974
  • 财政年份:
    2022
  • 资助金额:
    $ 33.11万
  • 项目类别:
Function of Chromatin Features in Cellular Programming
染色质特征在细胞编程中的作用
  • 批准号:
    10610383
  • 财政年份:
    2020
  • 资助金额:
    $ 33.11万
  • 项目类别:
Function of Chromatin Features in Cellular Programming
染色质特征在细胞编程中的作用
  • 批准号:
    10026479
  • 财政年份:
    2020
  • 资助金额:
    $ 33.11万
  • 项目类别:
Function of Chromatin Features in Cellular Programming
染色质特征在细胞编程中的作用
  • 批准号:
    10206199
  • 财政年份:
    2020
  • 资助金额:
    $ 33.11万
  • 项目类别:
Function of Chromatin Features in Cellular Programming
染色质特征在细胞编程中的作用
  • 批准号:
    10383776
  • 财政年份:
    2020
  • 资助金额:
    $ 33.11万
  • 项目类别:

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