RNA-mediated recruitment of epigenetic regulators

RNA介导的表观遗传调节因子的募集

• 批准号: 6903209
• 负责人: FRANK U SAUER
• 金额: $ 28.78万
• 依托单位: UNIVERSITY OF CALIFORNIA RIVERSIDE
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-04-01 至 2010-03-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6903209
• 关键词: Drosophilidae; RNA; RNA binding protein; RNA interference; cell proliferation; genetic disorder; genetic regulation; genetic regulatory element; mass spectrometry; nucleic acid structure; protein structure function; recombinant proteins; small interfering RNA

DESCRIPTION (provided by applicant): The establishment and maintenance of mitotically and meitotically stable, epigenetic, gene expression patterns are the hallmark of cell fate determination in metazoans and mistakes in the underlying mechanisms can result in cancerous cell growth. Our long-term goal is to elucidate the regulatory mechanisms directing epigenetic as a prerequisite for the development of diagnostic and therapeutic assays that detect and attenuate epigenetic-based diseases. The specific hypothesis behind the proposed research is that the target genes of epigenetic regulators transcribe non-coding RNA that bind and recruit epigenetic regulators. That hypothesis is based on the observations that 1) DMA elements targeted by epigenetic regulators (TRE-and-PRE-elements) are transcribed in vivo, 2) epigenetic regulators of the SET-module family interact with RNA transcribed from TRE- or PRE-elements, and 3) the transient transcription of TRE- and PRE-elements restores the interaction of epigenetic regulators with target genes in vivo. Based on these observations, the experimental focus of this proposal is on the role of non-coding RNA for the recruitment of epigenetic regulators to target genes. The specific aims are to: 1. Elucidate the role of non-coding RNA for the recruitment of epigenetic regulators. We will identify the protein- and RNA-motifs that mediate the interaction of RNA transcribed from TRE- and PRE-elements with epigenetic regulators and proteins that retain the RNA at TRE- and PRE-elements. 2. Identify novel interactions between epigenetic regulators and TRE- and PRE-transcripts. TRE- and PRE-elements serve as a target for various groups of epigenetic regulators, implying that RNA from those elements may recruit members of different families of epigenetic regulators. We will identify novel interactions between epigenetic regulators and RNA transcribed from TRE- and PRE-elements. 3. Dissection of the role and function of the interaction between epigenetic and non-coding RNA for development and disease. The recruitment of epigenetic regulators to target genes correlates with development and disease. We will correlate the transcription of RNA from TRE- and PRE-elements in cells and tissues with the recruitment of epigenetic regulators to target genes, cell fate determination in Drosophila, and the aberrant proliferation of mammalian cells.

描述（由申请人提供）：在有丝分裂和米特稳定的，表观遗传，基因表达模式的建立和维持是后生动物中细胞命运确定的标志，而基本机制中的错误可能会导致癌细胞的生长。我们的长期目标是阐明指导表观遗传学的调节机制，作为开发诊断和治疗测定法的先决条件，这些测定法检测并减弱了基于表观遗传的疾病。拟议的研究背后的特定假设是表观遗传调节剂的靶基因转录了结合和募集表观遗传调节剂的非编码RNA。 That hypothesis is based on the observations that 1) DMA elements targeted by epigenetic regulators (TRE-and-PRE-elements) are transcribed in vivo, 2) epigenetic regulators of the SET-module family interact with RNA transcribed from TRE- or PRE-elements, and 3) the transient transcription of TRE- and PRE-elements restores the interaction of epigenetic regulators with target genes in体内。基于这些观察结果，该提案的实验重点是非编码RNA在募集表观遗传调节剂靶向基因方面的作用。具体目的是： 1。阐明非编码RNA在募集表观遗传调节剂中的作用。我们将确定介导从TRE和预元素与表观遗传调节剂和蛋白质中的RNA相互作用的蛋白质和RNA-MOTIF，这些RNA在TRE和预元素上保留RNA。 2。确定表观遗传调节剂与转录和前转录之间的新型相互作用。 TRE和预元素是各种表观遗传调节剂的目标，这意味着这些元素的RNA可能会招募不同表观遗传调节剂的成员。我们将确定表观遗传调节剂与从TRE和预元素转录的RNA之间的新型相互作用。 3。解剖表观遗传和非编码RNA之间相互作用的作用和功能用于发育和疾病。表观遗传调节剂靶向基因的募集与发育和疾病有关。我们将将细胞和组织中RNA的RNA转录与表观遗传调节剂的募集到靶向基因，果蝇中的细胞命运测定以及哺乳动物细胞的异常增殖。