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Abstract：
Previous studies of the murine Ly49 and human KIR gene clusters implicated competing sense and antisense promoters in the control of variegated gene expression. In the current study, an examination of transcription factor genes defines an abundance of convergent and divergent sense/antisense promoter pairs, suggesting that competing promoters may control cell fate determination. Differentiation of CD34+ hematopoietic progenitors in vitro shows that cells with GATA1 antisense transcription have enhanced GATA2 transcription and a mast cell phenotype, whereas cells with GATA2 antisense transcription have increased GATA1 transcripts and an erythroblast phenotype. Detailed analyses of the AHR and RORC genes demonstrate the ability of competing promoters to act as binary switches and the association of antisense transcription with an immature/progenitor cell phenotype. These data indicate that alternative cell fates generated by promoter competition in lineage-determining transcription factors contribute to the programming of cell differentiation.
摘要：
先前对鼠Ly49和人KIR基因簇的研究涉及竞争性有义和反义启动子控制杂色基因表达。在目前的研究中,转录因子基因的检查定义了大量的会聚和发散的有义/反义启动子对，这表明竞争性启动子可以控制细胞命运的决定。CD34+造血祖细胞的体外分化表明，GATA1反义转录的细胞具有增强的GATA2转录和肥大细胞表型，而具有GATA2反义转录的细胞具有增加的GATA1转录物和红细胞表型。对AHR和RORC基因的详细分析证明了竞争性启动子充当二元开关的能力以及反义转录与未成熟/祖细胞表型的关联。这些数据表明，由谱系决定转录因子中的启动子竞争产生的替代细胞命运有助于细胞分化的编程。
