Systems-wide analysis of histone lysine 2-hydroxyisobutyrylation pathway

组蛋白赖氨酸 2-羟基异丁酰化途径的全系统分析

基本信息

  • 批准号:
    9458207
  • 负责人:
  • 金额:
    $ 44.9万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2016
  • 资助国家:
    美国
  • 起止时间:
    2016-06-20 至 2020-03-31
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): Histone post-translational modification (PTM, or histone mark) is critical to dynamic modulation of chromatin structure and function. Dysregulation of histone modification processes contributes to the development of many diseases, such as cancer, cardiovascular and neurological diseases. We recently reported a new, evolutionarily-conserved histone mark, lysine 2-hydroxyisobutyrylation (Khib). We showed that Khib is present among 63 histone lysine residues in both human and mouse, more than the known numbers of the widely studied histone acetylation (Kac) and methylation (Kme) sites. We also obtained multiple lines of evidence that suggest important and unique biological functions of histone Khib: this class of histone modification shows distinct genomic distributions from the widely studied histone Kac during male germ cell differentiation; it is associated with active gene transcription and H4K8hib is a better indicator for high gene expression than its corresponding H4K8ac; histone Khib can direct in vitro transcription in a manner dependent on 2-hydroxyisobutyryl CoA, suggesting that histone Khib impacts chromatin structure and transcriptional activity; histone Khib has different profiles between transcriptionally active and transcriptionally silent chromatin in Tetrahymena thermophile, in different cell cycle stages, and during mouse spermotogenesis. These results suggest that histone Khib is structurally and mechanistically different from histone Kac. The major players regulating histone Khib pathway would break new ground in epigenetic research and improve our understanding of cellular physiology and human disease. In the proposed research, we will study histone Khib pathway using an integrated approach. We will identify histone Khib-regulatory enzymes and direct binding proteins of histone Khib marks. We will also investigate genomic distributions of key histone Khib marks in mouse genome, and compare these data with those of the well-studied histone acetylation and methylation marks. Our team is well positioned to carry out this project, because of our extensive expertise in the areas of epigenomics, biochemistry, proteomics, stem cell biology, and the tremendous preliminary results we generated. This study will overcome a major hurdle to study biology of histone Khib pathway by revealing key regulatory elements and likely characterize novel epigenetic mechanisms, perhaps analogous to the characterization of histone Kac and Kme pathways.


项目成果

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会议论文数量(0)
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YINGMING ZHAO其他文献

YINGMING ZHAO的其他文献

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{{ truncateString('YINGMING ZHAO', 18)}}的其他基金

Systematic screening for new histone marks and studying their epigenetic function
系统筛选新组蛋白标记并研究其表观遗传功能
  • 批准号:
    10579280
  • 财政年份:
    2020
  • 资助金额:
    $ 44.9万
  • 项目类别:
Systematic screening for new histone marks and studying their epigenetic function
系统筛选新组蛋白标记并研究其表观遗传功能
  • 批准号:
    10401345
  • 财政年份:
    2020
  • 资助金额:
    $ 44.9万
  • 项目类别:
Biochemistry of lysine crotonylation pathway
赖氨酸巴豆酰化途径的生物化学
  • 批准号:
    8482624
  • 财政年份:
    2013
  • 资助金额:
    $ 44.9万
  • 项目类别:
Biochemistry of lysine crotonylation pathway
赖氨酸巴豆酰化途径的生物化学
  • 批准号:
    8654351
  • 财政年份:
    2013
  • 资助金额:
    $ 44.9万
  • 项目类别:
APPLICATION OF PTMAP2 FOR PROTEIN POSTTRANSLATIONAL MODIFICATION ANALYSIS
PTMAP2 在蛋白质翻译后修饰分析中的应用
  • 批准号:
    8364316
  • 财政年份:
    2011
  • 资助金额:
    $ 44.9万
  • 项目类别:
APPLICATION OF PTMAP2 FOR PROTEIN POSTTRANSLATIONAL MODIFICATION ANALYSIS
PTMAP2 在蛋白质翻译后修饰分析中的应用
  • 批准号:
    8171932
  • 财政年份:
    2010
  • 资助金额:
    $ 44.9万
  • 项目类别:
DEVELOPMENT OF PTMAP20 FOR GENOME-WIDE PROTEIN POSTTRANSLATIONAL MODIFICATION
用于全基因组蛋白质翻译后修饰的 PTMAP20 的开发
  • 批准号:
    8171905
  • 财政年份:
    2010
  • 资助金额:
    $ 44.9万
  • 项目类别:
DEVELOPMENT OF PTMAP20 FOR GENOME-WIDE PROTEIN POSTTRANSLATIONAL MODIFICATION
用于全基因组蛋白质翻译后修饰的 PTMAP20 的开发
  • 批准号:
    7956366
  • 财政年份:
    2009
  • 资助金额:
    $ 44.9万
  • 项目类别:
Systematic screening for new histone marks
系统筛选新的组蛋白标记
  • 批准号:
    7693723
  • 财政年份:
    2008
  • 资助金额:
    $ 44.9万
  • 项目类别:
Global characterization of lysine acetylation in cancer by a proteomics approach
通过蛋白质组学方法对癌症中赖氨酸乙酰化进行整体​​表征
  • 批准号:
    7817093
  • 财政年份:
    2008
  • 资助金额:
    $ 44.9万
  • 项目类别:

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