Nuclear Factor Y in Blood Differentiation

血液分化中的核因子Y

• 批准号: 7105431
• 负责人: ALISHA MOHAMED-HADLEY
• 金额: $ 3.06万
• 依托单位: TEMPLE UNIV OF THE COMMONWEALTH
• 依托单位国家: 美国
• 财政年份: 2005
• 资助国家: 美国
• 起止时间: 2005-08-01 至 2008-07-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7105431
• 关键词: DNA binding protein; RNA interference; bone marrow; cell differentiation; chromatin immunoprecipitation; cytogenetics; gel mobility shift assay; gene expression; gene induction /repression; genetic promoter element; interleukin 6; intermolecular interaction; laboratory mouse; myeloid stem cell; nuclear proteins; tissue /cell culture; transcription factor

DESCRIPTION (provided by applicant): To dissect the regulation of terminal myeloid differentiation, primary response (MyD) genes have been isolated and characterized. MyD genes play important roles in terminal differentiation, growth arrest and apoptosis. The molecular mechanisms for induction of MyD genes at the onset of terminal differentiation have not been elucidated. Activation of MyD genes by differentiation inducers has been studied using M1 myeloid leukemia cells and myeloid cells from bone marrow (BM). JunB was chosen as a paradigm to investigate the activation of MyD genes. The -651-52 JunB IL-6RE has been shown to be necessary and sufficient for JunB induction in M1 cells, and the transcription factor NF-Y binds to the CCAAT element within this region. The purpose of Aim I is to ascertain if the NF-Y complex binds to the JunB promoter in vivo prior to as well as following induction of myeloid differentiation, using chromatin immunoprecipitation (ChIP), as previously observed employing EMSA assays for M1 cells. This will be done using M1 cells and BM. Experiments are delineated in Aim II to establish a role for NF-Y in MyD gene induction and myeloid differentiation. This research plan will yield new information on the regulation of terminal myeloid differentiation, and breakdowns in these controls that can lead to leukemias and anemias, thereby generating tools to ultimately aid in the diagnosis, prognosis and rational therapeutic design for these disorders.

描述（由申请人提供）：为了剖析末端髓样分化的调节，主要反应（MYD）基因已被隔离和表征。 MyD基因在末端分化，生长停滞和凋亡中起着重要作用。尚未阐明在末端分化开始时诱导MyD基因的分子机制。通过分化诱导剂对MyD基因的激活已经使用M1髓样白血病细胞和骨髓（BM）的髓样细胞进行了研究。 JUNB被选为研究MyD基因激活的范例。 -651-52 JUNB IL-6RE已被证明是M1细胞中JUNB诱导的必要和足够的，并且转录因子NF-Y与该区域内的CCAAT元素结合。目的I的目的是确定NF-Y复合物在使用染色质免疫沉淀（CHIP）之前以及遵循髓样分化之前与JunB启动子结合，如先前观察到的M1细胞使用EMSA测定法。这将使用M1单元和BM完成。在AIM II中划定了实验，以确立NF-Y在MyD基因诱导和髓样分化中的作用。该研究计划将产生有关终末粒细胞分化的调节的新信息，以及这些控制中可能导致白血病和贫血的细分，从而生成工具，最终为这些疾病的诊断，预后和理性的治疗设计提供了帮助。