Molecular and genetic analysis of DP103

DP103的分子和遗传分析

• 批准号: 7056323
• 负责人: SVEN W HEINZ
• 金额: $ 5.04万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN DIEGO
• 依托单位国家: 美国
• 财政年份: 2006
• 资助国家: 美国
• 起止时间: 2006-12-01 至 2009-11-30
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7056323
• 关键词: apoptosis; cell differentiation; cell growth regulation; cell proliferation; developmental genetics; epigenetics; gene induction /repression; genetic library; helicase; hematopoiesis; laboratory mouse; macrophage; mammalian embryology; postdoctoral investigator; transcription factor; yeast two hybrid system

DESCRIPTION (provided by applicant): Differentiation of macrophages from precursor cells is accompanied by irreversible growth arrest, induced by stable transcriptional repression of cell cycle-associated genes. Inhibition of the mechanisms that cause GO arrest plays a central role in leukemogenesis. Growth arrest induced by mitogenic ets transcriptional suppressor (METS), which is upregulated during macrophage differentiation requires the DEAD box protein DP103 (DP103). DP103 also acts as a corepressor for a number of other, divergent transcription factors, which suggests a broad functional role for DP103 as a corepressor. Studies are proposed to define the developmental functions, transcriptional targets and repression mechanisms of DP103. Its possible role as a corepressor for a larger number of transcription factors will be assessed by identifying new interaction partners in a yeast two-hybrid screen of a macrophage cDNA library. To assess its function in embryonic development, in controlling proliferation during hematopoiesis, DP103 knockout mice will be generated and the proliferative potential of macrophages and macrophage precursors analyzed. Finally, the potentially epigenetic repression mechanism of DP103 will be analyzed by genome-wide location analysis.

描述（由申请人提供）：巨噬细胞从前体细胞分化伴随着不可逆的生长停滞，这是由细胞周期相关基因的稳定转录抑制诱导的。抑制导致GO停滞的机制在白血病发生中起着核心作用。由促有丝分裂ets转录抑制因子（METS）诱导的生长停滞（其在巨噬细胞分化期间上调）需要DEAD盒蛋白DP103（DP103）。DP103也作为一个辅阻遏物的数量，不同的转录因子，这表明了一个广泛的功能作用，DP103作为辅阻遏物。本文拟对DP103的发育功能、转录靶点和抑制机制进行研究。其可能的作用，作为一个corepressor的大量的转录因子将通过确定新的相互作用的合作伙伴在酵母双杂交筛选的巨噬细胞cDNA文库进行评估。为了评估其在胚胎发育中控制造血期间增殖的功能，将产生DP 103敲除小鼠并分析巨噬细胞和巨噬细胞前体的增殖潜力。最后，DP103的潜在表观遗传抑制机制将通过全基因组定位分析进行分析。