CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing.

CCAAT/enhancer binding protein epsilon is preferentially up-regulated during granulocytic differentiation and its functional versatility is determined by alternative use of promoters and differential splicing.
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CCAAT/增强子结合蛋白ε在粒细胞分化过程中优先上调,其功能多样性由启动子的选择性使用和差异剪接决定。

DOI:
10.1073/pnas.94.12.6462
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发表时间:
1997
影响因子:
11.1
通讯作者:
Xanthopoulos,KG
Xanthopoulos,KG
中科院分区:
综合性期刊1区
文献类型:
--
作者:
Yamanaka,R;Kim,GD;Radomska,HS;Lekstrom-Himes,J;Smith,LT;Antonson,P;Tenen,DG;Xanthopoulos,KG

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CCAAT/增强子结合蛋白(C/EBP)是最近克隆的C/EBP家族转录因子的成员,并且仅在造血来源的细胞中表达。人C/EBP β基因由两个交替启动子Pα和Pβ转录。差异剪接和启动子的交替使用的组合产生大小为2.6kb和1.3- 1.5kb的四种mRNA同种型。这些转录本可以编码三种蛋白质,计算分子量为32.2 kDa,27.8 kDa和14.3 kDa。因此,用对DNA结合结构域具有特异性的抗体进行蛋白质印迹,这是所有形式所共有的,可以鉴定多种蛋白质。人原代CD 34+细胞在体外粒系分化过程中,C/EBP mRNA表达明显上调。视黄酸处理HL 60早幼粒细胞白血病细胞24小时诱导C/EBP β mRNA水平的4倍,而延长治疗逐渐降低mRNA表达的预处理水平。瞬时转染实验与表达载体的两个亚型表明,32.2-kDa的蛋白质是一个激活剂的粒细胞集落刺激因子受体启动子的转录,而14.3-kDa的蛋白质不是。因此,C/EBP β以复杂的方式调节,并可能在参与骨髓分化的基因的调节中发挥作用。
CCAAT/enhancer binding protein (C/EBP) ɛ is a recently cloned member of the C/EBP family of transcription factors and is expressed exclusively in cells of hematopoietic origin. The human C/EBPɛ gene is transcribed by two alternative promoters, Pα and Pβ. A combination of differential splicing and alternative use of promoters generates four mRNA isoforms, of 2.6 kb and 1.3–1.5 kb in size. These transcripts can encode three proteins of calculated molecular mass 32.2 kDa, 27.8 kDa, and 14.3 kDa. Accordingly, Western blots with antibodies specific for the DNA-binding domain, that is common to all forms, identify multiple proteins. C/EBPɛ mRNA was greatly induced duringin vitrogranulocytic differentiation of human primary CD34+cells. Retinoic acid treatment of HL60 promyelocytic leukemia cells for 24 hr induced C/EBPɛ mRNA levels by 4-fold, while prolonged treatment gradually reduced mRNA expression to pretreatment levels. Transient transfection experiments with expression vectors for two of the isoforms demonstrated that the 32.2-kDa protein is an activator of transcription of granulocyte colony-stimulating factor receptor promoter, while the 14.3-kDa protein is not. Thus, C/EBPɛ is regulated in a complex fashion and may play a role in the regulation of genes involved in myeloid differentiation.
DOI: --
发表时间: 1989
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影响因子: 10.5
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期刊: European journal of biochemistry
影响因子: --
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期刊: BLOOD
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