Blank V, Kim M J, Andrews N C
Howard Hughes Medical Institute, Children's Hospital, and Harvard Medical School, Boston, MA 02115, USA.
Blood. 1997 Jun 1;89(11):3925-35.
Mammalian globin gene expression is activated through NF-E2 elements recognized by basic-leucine zipper proteins of the AP-1 superfamily. The specificity of NF-E2 DNA binding is determined by several nucleotides adjacent to a core AP-1 motif, comprising a recognition site for transcription factors of the Maf subfamily. Earlier work proposed that p18(MafK) forms a heterodimer with hematopoietic-specific protein p45 NF-E2 to activate transcription through NF-E2 sites. However, there was no direct evidence that p18(MafK) serves this function in vivo; in fact, mice lacking p18(MafK) have no phenotype. Here we describe a novel cDNA clone that encodes the human homolog of chicken MafG. Human MafG heterodimerizes with p45 NF-E2 and binds DNA with specificity identical to that of purified NF-E2 DNA binding activity. A tethered heterodimer of p45 and MafG is fully functional in supporting expression of alpha- and beta-globin, and in promoting erythroid differentiation in CB3, a p45-deficient mouse erythroleukemia cell line. These results indicate that human MafG can serve as a functional partner for p45 NF-E2, and suggest that the p45/MafG heterodimer plays a role in the regulation of erythropoiesis.
哺乳动物珠蛋白基因的表达是通过AP-1超家族的碱性亮氨酸拉链蛋白识别的NF-E2元件来激活的。NF-E2与DNA结合的特异性由核心AP-1基序附近的几个核苷酸决定，该基序包含Maf亚家族转录因子的识别位点。早期的研究提出，p18（MafK）与造血特异性蛋白p45 NF-E2形成异二聚体，通过NF-E2位点激活转录。然而，没有直接证据表明p18（MafK）在体内发挥这种功能；事实上，缺乏p18（MafK）的小鼠没有表型。在这里，我们描述了一个新的cDNA克隆，它编码鸡MafG的人类同源物。人类MafG与p45 NF-E2异二聚化，并以与纯化的NF-E2 DNA结合活性相同的特异性结合DNA。p45和MafG的拴系异二聚体在支持α和β珠蛋白的表达以及促进CB3（一种p45缺陷的小鼠红白血病细胞系）的红系分化方面具有完全功能。这些结果表明，人类MafG可以作为p45 NF-E2的功能伙伴，并表明p45/MafG异二聚体在红细胞生成的调节中起作用。
