C/EBPb and heterochromatin: their role in adipogenesis

C/EBPb 和异染色质:它们在脂肪生成中的作用

基本信息

  • 批准号:
    8053414
  • 负责人:
  • 金额:
    $ 3.22万
  • 依托单位:
  • 依托单位国家:
    美国
  • 项目类别:
  • 财政年份:
    2009
  • 资助国家:
    美国
  • 起止时间:
    2009-04-08 至 2012-03-31
  • 项目状态:
    已结题

项目摘要

DESCRIPTION (provided by applicant): Obesity is one of the most prevalent health problems in the world, particularly if it is considered in relation to the increase in prevalence of associated diseases such as type II diabetes, dyslipemia and hypertension. Obesity is the consequence of increased adipocyte size as well as development of new fat cells. Adipogenesis results from a cascade of genetic events in which CCAAT/Enhancer Binding proteins (C/EBPs) play a key role. Disruption of the C/EBP2, C/EBP4 or C/EBP1 gene in mice causes defective development of adipose tissue. During adipogenesis the activation of a specific subset of genes and silencing of the remainder takes place. As genes are silenced, the extent of chromatin condensation increases, and extended regions of DNA are packaged in transcriptionally inactive form: heterochromatin. The organization of genes into heterochromatin is one of the mechanisms that control its silencing. Intriguingly, C/EBP2 rapidly relocalizes in heterochromatin upon hormonal stimulation. C/EBP2, C/EBP4 and C/EBP1 also concentrate in heterochromatin upon induction of preadipocytes to differentiate into adipocytes. We hypothesize that C/EBP2 may play a role in the regulation of gene silencing during cellular differentiation. Thus the specific aims of this project are to investigate in preadipocytes and during adipogenesis: a) mechanisms that regulate the formation of homo- and heterodimers of C/EBP2, b) mechanisms that control the subnuclear distribution of C/EBP2, and c) the role of C/EBP2 in gene expression by determining the position of C/EBP2 target genes with respect to heterochromatin. Our studies will provide insight into the understanding of the mechanism that controls the nuclear redistribution of C/EBPs and their role in the heterochromatic nuclear compartment. Improvement of our understanding of adipogenesis is important, for it will ultimately contribute to the development of new therapeutic strategies for obesity and related disorders. This study extends new approaches initiated by Dr. Piwien-Pilipuk when she was a postdoctoral trainee in Dr. Schwartz's lab. Now that Dr. Piwien-Pilipuk has returned to Argentina and is establishing an independent lab, the collaborative interactions between these PI's through the proposed project, involving visits to Dr. Schwartz's lab by Dr. Piwien-Pilipuk and at least one of her graduate students during the course of this project, will facilitate Dr. Piwien-Pilipuk's career development, in addition to adding to understanding of the regulation of C/EBP beta through collaborative papers. This research will be done primarily at Instituto Leloir, Buenos Aires, Argentina as an extension of NIH Grant R01DK46072 to Dr. Schwartz PUBLIC HEALTH RELEVANCE: Obesity is one of the most prevalent health problems in the world, particularly if it considered in relation to associated diseases such as diabetes. Improvement of our understanding of adipogenesis will ultimately contribute to the development of new therapeutic strategies for obesity and related disorders.
描述(由申请人提供):肥胖是世界上最普遍的健康问题之一,特别是如果考虑到它与 II 型糖尿病、血脂异常和高血压等相关疾病的患病率增加有关。肥胖是脂肪细胞大小增加以及新脂肪细胞发育的结果。脂肪生成是一系列遗传事件的结果,其中 CCAAT/增强子结合蛋白 (C/EBP) 发挥着关键作用。小鼠 C/EBP2、C/EBP4 或 C/EBP1 基因的破坏会导致脂肪组织发育缺陷。在脂肪形成过程中,会发生特定基因子集的激活和其余基因的沉默。随着基因沉默,染色质浓缩程度增加,DNA 的延伸区域以转录非活性形式包装:异染色质。将基因组织成异染色质是控制其沉默的机制之一。有趣的是,C/EBP2 在激素刺激下迅速重新定位到异染色质中。在诱导前脂肪细胞分化为脂肪细胞时,C/EBP2、C/EBP4 和 C/EBP1 也集中在异染色质中。我们假设 C/EBP2 可能在细胞分化过程中基因沉默的调节中发挥作用。因此,该项目的具体目标是研究前脂肪细胞和脂肪生成过程中的:a) 调节 C/EBP2 同二聚体和异二聚体形成的机制,b) 控制 C/EBP2 亚核分布的机制,以及 c) 通过确定 C/EBP2 靶基因相对于异染色质的位置来研究 C/EBP2 在基因表达中的作用。我们的研究将深入了解控制 C/EBP 核重新分布的机制及其在异染色质核区室中的作用。提高我们对脂肪生成的理解非常重要,因为它将最终有助于开发肥胖及相关疾病的新治疗策略。这项研究扩展了 Piwien-Pilipuk 博士在 Schwartz 博士实验室担任博士后实习生时发起的新方法。现在 Piwien-Pilipuk 博士已返回阿根廷并正在建立一个独立的实验室,这些 PI 之间通过拟议项目进行的协作互动,包括 Piwien-Pilipuk 博士和至少一名研究生在该项目期间访问 Schwartz 博士的实验室,将促进 Piwien-Pilipuk 博士的职业发展,此外还可以通过以下方式加深对 C/EBP beta 监管的理解: 合作论文。这项研究将主要在阿根廷布宜诺斯艾利斯的勒卢瓦研究所进行,作为 NIH 拨款 R01DK46072 给 Schwartz 博士的延伸。 公共健康相关性:肥胖是世界上最普遍的健康问题之一,特别是如果考虑到与糖尿病等相关疾病的关系。提高我们对脂肪生成的理解最终将有助于开发肥胖及相关疾病的新治疗策略。

项目成果

期刊论文数量(3)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
Dynamic mitochondrial-nuclear redistribution of the immunophilin FKBP51 is regulated by the PKA signaling pathway to control gene expression during adipocyte differentiation.
亲免素 FKBP51 的动态线粒体-核重新分布受 PKA 信号通路调节,以控制脂肪细胞分化过程中的基因表达。
  • DOI:
    10.1242/jcs.125799
  • 发表时间:
    2013
  • 期刊:
  • 影响因子:
    4
  • 作者:
    Toneatto,Judith;Guber,Sergio;Charó,NancyL;Susperreguy,Sebastián;Schwartz,Jessica;Galigniana,MarioD;Piwien-Pilipuk,Graciela
  • 通讯作者:
    Piwien-Pilipuk,Graciela
Management of cytoskeleton architecture by molecular chaperones and immunophilins.
  • DOI:
    10.1016/j.cellsig.2011.07.023
  • 发表时间:
    2011-12
  • 期刊:
  • 影响因子:
    4.8
  • 作者:
    Quintá HR;Galigniana NM;Erlejman AG;Lagadari M;Piwien-Pilipuk G;Galigniana MD
  • 通讯作者:
    Galigniana MD
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Jessica Schwartz其他文献

Jessica Schwartz的其他文献

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{{ truncateString('Jessica Schwartz', 18)}}的其他基金

Growth Hormone Signaling to the Nucleus
生长激素向细胞核发出信号
  • 批准号:
    7992528
  • 财政年份:
    2010
  • 资助金额:
    $ 3.22万
  • 项目类别:
C/EBPb and heterochromatin: their role in adipogenesis
C/EBPb 和异染色质:它们在脂肪生成中的作用
  • 批准号:
    7629396
  • 财政年份:
    2009
  • 资助金额:
    $ 3.22万
  • 项目类别:
C/EBPb and heterochromatin: their role in adipogenesis
C/EBPb 和异染色质:它们在脂肪生成中的作用
  • 批准号:
    7806403
  • 财政年份:
    2009
  • 资助金额:
    $ 3.22万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY GROWTH HORMONE & RELATED GROWTH FACTORS
生长激素对基因表达的调节
  • 批准号:
    6263646
  • 财政年份:
    1998
  • 资助金额:
    $ 3.22万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY GROWTH HORMONE & RELATED GROWTH FACTORS
生长激素对基因表达的调节
  • 批准号:
    6297003
  • 财政年份:
    1998
  • 资助金额:
    $ 3.22万
  • 项目类别:
REGULATION OF GENE EXPRESSION BY GROWTH HORMONE AND RELATED GROWTH FACTORS
生长激素和相关生长因子对基因表达的调节
  • 批准号:
    6244557
  • 财政年份:
    1997
  • 资助金额:
    $ 3.22万
  • 项目类别:
GROWTH HORMONE SIGNALING TO THE NUCLEUS
生长激素向细胞核发出信号
  • 批准号:
    6380767
  • 财政年份:
    1996
  • 资助金额:
    $ 3.22万
  • 项目类别:
Growth Hormone Signaling to the Nucleus
生长激素向细胞核发出信号
  • 批准号:
    7092773
  • 财政年份:
    1996
  • 资助金额:
    $ 3.22万
  • 项目类别:
GROWTH HORMONE SIGNALING TO THE NUCLEUS
生长激素向细胞核发出信号
  • 批准号:
    2444080
  • 财政年份:
    1996
  • 资助金额:
    $ 3.22万
  • 项目类别:
GROWTH HORMONE SIGNALING TO THE NUCLEUS
生长激素向细胞核发出信号
  • 批准号:
    6194865
  • 财政年份:
    1996
  • 资助金额:
    $ 3.22万
  • 项目类别:

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