NEUTROPHILS AND MONOCYTES EXPRESS HIGH-LEVELS OF PU.1 (SPI-1) BUT NOT SPI-B
NEUTROPHILS AND MONOCYTES EXPRESS HIGH-LEVELS OF PU.1 (SPI-1) BUT NOT SPI-B
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DOI：
10.1182/blood.v85.10.2918.bloodjournal85102918
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发表时间：
1995-05-15
期刊：
影响因子：
20.3
通讯作者：
TENEN, DG
中科院分区：
文献类型：
--
作者：
CHEN, HM;ZHANG, P;TENEN, DG
PU.1(SPI-1癌基因)和SPI-B是Ets转录因子家族中密切相关的成员，由相似的DNA结合域介导具有相似的DNA结合特异性。PU1和SPI-B主要在巨噬细胞和B细胞中协同表达，但在早期造血细胞和髓系向单核/巨噬细胞或中性粒细胞分化过程中的表达尚未被广泛研究。在此，我们报道了PU.1在人纯化的CD34(+)细胞和小鼠多潜能FDCP-Mix A4细胞的髓系分化过程中上调，提示PU.1是多潜能祖细胞分化过程中的早期事件。在髓系细胞系U937和HL-60向单核细胞和中性粒细胞分化的过程中，PU.1的表达保持在稳定的水平。PU.1在成熟人单核细胞和人外周血中性粒细胞中的表达水平最高。与PU.1相反，SPI-B的mRNA和蛋白只在一些B细胞系和脾中发现，而在髓系细胞系、中性粒细胞和巨噬细胞中没有发现。体外翻译的SPI-B蛋白可与髓系启动子中的PU1结合，并在非髓系细胞中反式激活这些启动子。因此，尽管PU.1和SPI-B可能与相似的DNA调控元件结合，并在体外具有转录激活功能的冗余，但由于髓系细胞中缺乏显著水平的SPI-B，因此SPI-B不太可能在髓系发育和基因表达中发挥重要作用。相反，PU.1不仅在单核细胞和巨噬细胞中高水平表达，而且在中性粒细胞中也高水平表达，这表明PU.1可以激活两种主要髓系的基因表达。(C)1995年由美国血液病学会主办。
PU.1 (the Spi-1 oncogene) and Spi-B are closely related members of the ets transcription factor family, sharing similar DNA binding specificities mediated by similar DNA binding domains. PU.1 and Spi-B have been previously described as being predominantly expressed coordinately in macrophages and B cells, but their expression in early hematopoietic stages and during the course of myeloid differentiation to monocytes and macrophages or to neutrophils has not been extensively investigated. Here, we report that PU.1 mRNA is upregulated during myeloid differentiation of human purified CD34(+) cells and murine multipotential FDCP-mix A4 cells, suggesting that PU.1 is upregulated as an early event during differentiation of multipotential progenitor cells. PU.1 expression is maintained at stable levels during differentiation of myeloid cell lines U937 and HL-60 to monocytic and neutrophilic cells. PU.1 is expressed at highest levels in mature human monocytes and human peripheral blood neutrophils. In contrast to PU.1, significant levels of Spi-B mRNA and protein are found only in some B-cell lines and spleen but are not found in myeloid cell lines, neutrophils, or macrophages. In vitro translated Spi-B protein can bind to PU.1 binding sites in myeloid promoters and transactivate these promoters in nonmyeloid cells. Therefore, although PU.1 and Spi-B may bind to similar DNA control elements and have redundancy of transactivation function in vitro, the lack of significant levels of Spi-B in myeloid cells makes it unlikely that Spi-B plays a significant role in myeloid lineage development and gene expression. In contrast, PU.1 is expressed at high levels not only in monocytes and macrophages but also in neutrophils, indicating that PU.1 can activate gene expression in both major myeloid lineages. (C) 1995 by The American Society of Hematology.