Metabolic Control of Puberty: Epigenetic Links

青春期的代谢控制:表观遗传联系

基本信息

  • 批准号:
    9477692
  • 负责人:
  • 金额:
    $ 48.23万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2015
  • 资助国家:
    美国
  • 起止时间:
    2015-07-10 至 2020-04-30
  • 项目状态:
    已结题

项目摘要

 DESCRIPTION (provided by applicant): It has been known for years that energy balance can be permanently affected by nutritional challenges taking place during a critical period of "developmental programming", which in humans occurs during late gestation and in rodents during early post-natal life. It is also well established that these alterations affect female neuroendocrine reproductive development; increased nutritional availability advances the timing of puberty, and nutritional deficiency delays it. Perhaps due to the complexity of the systems involved and the lack of definitive candidates, neither the molecules linking nutritional programming to pubertal development nor the puberty-related genes they may regulate have been identified. We recently discovered that female puberty is regulated by an epigenetic mechanism that involves lifting of a transcriptional repressive tone exerted by the Polycomb group (PcG) of transcriptional silencers, and that this repression is imposed on downstream genes involved in the stimulatory control of GnRH secretion (epitomized by the Kiss1 gene).By discovering a novel epigenetic mechanism controlling the timing of puberty and identifying its basic components, we have now unveiled the existence of a regulatory system that may not only fulfill the long-sought out role of linking nutrition to neuroendocrine reproductive development, but is also amenable to experimental scrutiny. Accordingly, this proposal will test the hypothesis that alterations in the developmental programming of energy balance affect the timing of puberty by regulating the mechanism of epigenetic silencing that keeps GnRH secretion in check during prepubertal maturation. To this end, the following hypotheses will be tested: 1) That altering nutrient availability during early postnatal life affects puberty by regulating an epigenetic repressive tone imposed by the PcG complex on puberty-activating (PA) genes. 2) That additional PcG target genes potentially relevant to the timing of puberty and to the nutritional regulation of this process can be identified by epigenome-wide anlaysis using RNA-and ChIP- massively parallel sequencing technology; and 3) That one of the epigenetic link connecting nutrition to pubertal development is SIRT1, a fuel-sensing molecule that according to our hypothesis would function as a biological rheostat to silence/derepress PA genes in response to early nutritional unbalance. We anticipate that a successful outcome of the proposed studies will provide major insights into the integrative mechanisms linking energy homeostasis, the neuroendocrine brain and the control of puberty. We also anticipate that these studies will significantly enhance our understanding of how disorders in energy balance influence the timing and progression of puberty, and will make researchers and clinicians aware of the epigenetics contribution to these disorders.
 描述(由申请人提供):多年来,人们已经知道能量平衡可能会受到“发育规划”关键时期发生的营养挑战的永久影响,这种情况发生在人类妊娠晚期和啮齿类动物产后早期。众所周知,这些改变会影响女性神经内分泌生殖发育。营养供应的增加会提前青春期的到来,而营养缺乏则会延迟青春期的到来。也许由于所涉及系统的复杂性和缺乏明确的候选者,将营养规划与青春期发育联系起来的分子以及它们可能调节的青春期相关基因都尚未被识别。我们最近发现,女性青春期受到表观遗传机制的调节,该机制涉及转录沉默子多梳组(PcG)施加的转录抑制音的解除,并且这种抑制作用于参与 GnRH 分泌刺激控制的下游基因(以 Kiss1 基因为代表)。 就其基本组成部分而言,我们现在已经揭示了一个监管系统的存在,该系统不仅可以实现长期寻求的将营养与神经内分泌生殖发育联系起来的作用,而且还可以接受实验审查。因此,该提案将检验以下假设:能量平衡发育编程的改变通过调节表观遗传沉默机制影响青春期的时间,表观遗传沉默机制在青春期前成熟期间控制 GnRH 分泌。为此,将测试以下假设: 1) 改变出生后早期的营养可用性会通过调节 PcG 复合物对青春期激活 (PA) 基因施加的表观遗传抑制音来影响青春期。 2) 可以使用 RNA 和 ChIP 大规模并行测序技术通过表观基因组分析来鉴定与青春期时间和该过程的营养调节潜在相关的其他 PcG 靶基因; 3) 连接营养与青春期发育的表观遗传联系之一是 SIRT1,这是一种燃料感应分子,根据我们的假设,它可以充当生物变阻器,沉默/去抑制 PA 基因,以应对早期营养失衡。我们预计,拟议研究的成功结果将为能量稳态、大脑神经内分泌和青春期控制之间的整合机制提供重要见解。我们还预计这些研究将显着增强我们对能量平衡紊乱如何影响青春期时间和进展的理解,并使研究人员和临床医生意识到表观遗传学对这些疾病的影响。

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 }}

Alejandro Lomniczi其他文献

Alejandro Lomniczi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('Alejandro Lomniczi', 18)}}的其他基金

Epigenetic Signaling in the Aging Hypothalamus
衰老下丘脑的表观遗传信号
  • 批准号:
    10056001
  • 财政年份:
    2020
  • 资助金额:
    $ 48.23万
  • 项目类别:
Epigenetic Signaling in the Aging Hypothalamus
衰老下丘脑的表观遗传信号
  • 批准号:
    10227244
  • 财政年份:
    2020
  • 资助金额:
    $ 48.23万
  • 项目类别:
Metabolic Control of Puberty: Epigenetic Links
青春期的代谢控制:表观遗传联系
  • 批准号:
    8940852
  • 财政年份:
    2015
  • 资助金额:
    $ 48.23万
  • 项目类别:
Metabolic Control of Puberty: Epigenetic Links
青春期的代谢控制:表观遗传联系
  • 批准号:
    9270429
  • 财政年份:
    2015
  • 资助金额:
    $ 48.23万
  • 项目类别:
USING SYSTEMS BIOLOGY TO UNDERSTAND POLYGENIC CONTROL OF PRIMATE PUBERTY
利用系统生物学了解灵长类青春期的多基因控制
  • 批准号:
    7715953
  • 财政年份:
    2008
  • 资助金额:
    $ 48.23万
  • 项目类别:
USING SYSTEMS BIOLOGY TO UNDERSTAND POLYGENIC CONTROL OF PRIMATE PUBERTY
利用系统生物学了解灵长类青春期的多基因控制
  • 批准号:
    7561986
  • 财政年份:
    2007
  • 资助金额:
    $ 48.23万
  • 项目类别:

相似海外基金

RII Track-4:NSF: From the Ground Up to the Air Above Coastal Dunes: How Groundwater and Evaporation Affect the Mechanism of Wind Erosion
RII Track-4:NSF:从地面到沿海沙丘上方的空气:地下水和蒸发如何影响风蚀机制
  • 批准号:
    2327346
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Standard Grant
BRC-BIO: Establishing Astrangia poculata as a study system to understand how multi-partner symbiotic interactions affect pathogen response in cnidarians
BRC-BIO:建立 Astrangia poculata 作为研究系统,以了解多伙伴共生相互作用如何影响刺胞动物的病原体反应
  • 批准号:
    2312555
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Standard Grant
How Does Particle Material Properties Insoluble and Partially Soluble Affect Sensory Perception Of Fat based Products
不溶性和部分可溶的颗粒材料特性如何影响脂肪基产品的感官知觉
  • 批准号:
    BB/Z514391/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Training Grant
Graduating in Austerity: Do Welfare Cuts Affect the Career Path of University Students?
紧缩毕业:福利削减会影响大学生的职业道路吗?
  • 批准号:
    ES/Z502595/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Fellowship
Insecure lives and the policy disconnect: How multiple insecurities affect Levelling Up and what joined-up policy can do to help
不安全的生活和政策脱节:多种不安全因素如何影响升级以及联合政策可以提供哪些帮助
  • 批准号:
    ES/Z000149/1
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Research Grant
感性個人差指標 Affect-X の構築とビスポークAIサービスの基盤確立
建立个人敏感度指数 Affect-X 并为定制人工智能服务奠定基础
  • 批准号:
    23K24936
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Grant-in-Aid for Scientific Research (B)
How does metal binding affect the function of proteins targeted by a devastating pathogen of cereal crops?
金属结合如何影响谷类作物毁灭性病原体靶向的蛋白质的功能?
  • 批准号:
    2901648
  • 财政年份:
    2024
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Studentship
ERI: Developing a Trust-supporting Design Framework with Affect for Human-AI Collaboration
ERI:开发一个支持信任的设计框架,影响人类与人工智能的协作
  • 批准号:
    2301846
  • 财政年份:
    2023
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Standard Grant
Investigating how double-negative T cells affect anti-leukemic and GvHD-inducing activities of conventional T cells
研究双阴性 T 细胞如何影响传统 T 细胞的抗白血病和 GvHD 诱导活性
  • 批准号:
    488039
  • 财政年份:
    2023
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Operating Grants
How motor impairments due to neurodegenerative diseases affect masticatory movements
神经退行性疾病引起的运动障碍如何影响咀嚼运动
  • 批准号:
    23K16076
  • 财政年份:
    2023
  • 资助金额:
    $ 48.23万
  • 项目类别:
    Grant-in-Aid for Early-Career Scientists
{{ showInfoDetail.title }}

作者:{{ showInfoDetail.author }}

知道了