...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Molecular and Cellular Biology >FKLF, a Novel Krüppel-Like Factor That Activates Human Embryonic and Fetal β-Like Globin Genes
【24h】

FKLF, a Novel Krüppel-Like Factor That Activates Human Embryonic and Fetal β-Like Globin Genes

机译：FKLF，一种新型的克虏伯样因子，可激活人胚和胎儿β样球蛋白基因

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

A cDNA encoding a novel Krüppel-type zinc finger protein, FKLF, was cloned from fetal globin-expressing human fetal erythroid cells. The deduced polypeptide sequence composed of 512 amino acids revealed that, like Sp1 and EKLF, FKLF has three contiguous zinc fingers at the near carboxyl-terminal end. A long amino-terminal domain is characterized by the presence of two acidic and two proline-rich regions. Reverse transcription (RT)-PCR assays using various cell lines demonstrated that the FKLF mRNA is expressed predominantly in erythroid cells. FKLF message is detectable by RT-PCR in fetal liver but not in adult bone marrow cells. As predicted from its structural features, FKLF is a transcriptional activator. In luciferase assays FKLF activated the γ- and ?-globin gene promoters, and, to a much lower degree, the β-globin promoter. Studies of HS2-γ gene reporter constructs carrying CACCC box deletions revealed that the CACCC box sequence of the γ gene promoter mediates the activation of the γ gene by FKLF. Other erythroid promoters (GATA-1, glycophorin B, ferrochelatase, porphobilinogen deaminase, and 5-aminolevulinate synthase) containing CACCC elements or GC-rich potential Sp1-binding sites were activated minimally, if at all, by FKLF, indicating that FKLF is not a general activator of genes carrying the CACCC motifs. Transfection of K562 cells with FKLF cDNA enhanced the expression of the endogenous ?- and γ-globin genes, suggesting an in vivo role of FKLF in fetal and embryonic globin gene expression. Our results indicate that the protein potentially encoded by the FKLF cDNA acts as a transcriptional activator of embryonic and fetal β-like globin genes.
机译：从表达胎儿珠蛋白的人胎儿红系细胞中克隆了一种编码新型克虏伯型锌指蛋白FKLF的cDNA。推导的由512个氨基酸组成的多肽序列显示，与Sp1和EKLF一样，FKLF在羧基末端附近具有三个连续的锌指。长氨基末端结构域的特征在于存在两个酸性和两个富含脯氨酸的区域。使用各种细胞系的逆转录（RT）-PCR分析表明FKLF mRNA主要在类红细胞中表达。通过RT-PCR在胎儿肝脏中可检测到FKLF信息，而在成年骨髓细胞中则无法检测到。从其结构特征可以预测，FKLF是转录激活因子。在荧光素酶测定中，FKLF激活了γ和γ珠蛋白基因启动子，并在较低的程度上激活了β珠蛋白启动子。对带有CACCC框缺失的HS2-γ基因报告基因构建体的研究表明，γ基因启动子的CACCC框序列介导了FKLF对γ基因的激活。包含CACCC元素或富含GC的潜在Sp1结合位点的其他类红系启动子（GATA-1，糖蛋白B，铁螯合酶，胆色素原脱氨酶和5-氨基乙酰丙酸合酶）被FKLF激活的程度最小，表明FKLF不是携带CACCC基序的基因的一般激活剂。用FKLF cDNA转染K562细胞可增强内源性β-和γ-球蛋白基因的表达，这表明FKLF在胎儿和胚胎球蛋白基因表达中具有体内作用。我们的结果表明，由FKLF cDNA潜在编码的蛋白质可充当胚胎和胎儿β样球蛋白基因的转录激活因子。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号