Molecular and genetic analysis of DP103

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，由细胞周期相关基因的稳定转录抑制诱导。抑制导致氧化石墨烯阻滞的机制在白血病发生中起着核心作用。巨噬细胞分化过程中表达上调的有丝分裂ets转录抑制因子（METS）诱导的生长停滞需要DEAD box蛋白DP103 （DP103）。DP103还作为许多其他发散性转录因子的辅抑制因子，这表明DP103作为辅抑制因子具有广泛的功能作用。对DP103的发育功能、转录靶点和抑制机制进行了进一步的研究。通过在巨噬细胞cDNA文库的酵母双杂交筛选中鉴定新的相互作用伙伴，将评估其作为大量转录因子的辅助抑制因子的可能作用。为了评估其在胚胎发育中的功能，在造血过程中控制增殖，将产生DP103基因敲除小鼠，并分析巨噬细胞和巨噬细胞前体的增殖潜能。最后，通过全基因组定位分析分析DP103潜在的表观遗传抑制机制。

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.