Mitsuma Ayako, Asano Haruhiko, Kinoshita Tomohiro, Murate Takashi, Saito Hidehiko, Stamatoyannopoulos George, Naoe Tomoki
Department of Hematology, Nagoya University Graduate School of Medicine, Nagoya, Japan.
Biochim Biophys Acta. 2005 Feb 14;1727(2):125-33. doi: 10.1016/j.bbaexp.2004.12.007.
FKLF-2 (KLF13) was cloned from fetal globin-expressing tissues and has been shown to be abundantly expressed in erythroid cells. In this study we examined the transcriptional regulation of the KLF13 gene. A 5.5 kb 5' flanking region cloned from mouse erythroleukemia (MEL) cell genomic DNA showed that major cis regulatory activities exist in the 550 bp sequence to the unique transcription start site, and that the promoter is more active in K562 cells than in COS-7 cells. The promoter was trans-activated by co-expressed GATA-1 through the sequence containing two CCAAT motifs, suggesting that GATA-1 is involved in the abundant expression of KLF13 mRNA in the erythroid tissue. Dual action, i.e. activating effect in COS-7 and repressive effect in K562 cell, was observed on its own promoter, suggesting a feedback mechanism for the transcriptional control of the KLF13 gene in the erythroid environment. These findings provide an insight on the mechanism of inducible mRNA expression of the KLF13 gene in erythroid cells.
FKLF-2(KLF13)是从表达胎儿珠蛋白的组织中克隆出来的,并且已证实在红系细胞中大量表达。在本研究中,我们检测了KLF13基因的转录调控。从小鼠红白血病(MEL)细胞基因组DNA中克隆出的一个5.5 kb的5'侧翼区域显示,主要的顺式调控活性存在于距唯一转录起始位点550 bp的序列中,并且该启动子在K562细胞中比在COS-7细胞中更具活性。该启动子通过共表达的GATA-1经包含两个CCAAT基序的序列而被反式激活,这表明GATA-1参与了红系组织中KLF13 mRNA的大量表达。在其自身启动子上观察到了双重作用,即在COS-7细胞中的激活作用和在K562细胞中的抑制作用,这表明在红系环境中KLF13基因的转录调控存在一种反馈机制。这些发现为红系细胞中KLF13基因诱导性mRNA表达的机制提供了见解。