Aronheim A, Shiran R, Rosen A, Walker M D
Biochemistry Department, Weizmann Institute of Science, Rehovot, Israel.
Proc Natl Acad Sci U S A. 1993 Sep 1;90(17):8063-7. doi: 10.1073/pnas.90.17.8063.
The E2A gene encodes transcription factors of the helix-loop-helix (HLH) family which are implicated in cell-specific transcriptional control in several cell lineages, including pancreatic beta cells. In the present work, we show by deletion mapping of both the E2A protein itself and the Gal4-E2A fusion protein that the protein contains at least two distinct activation domains. One domain (located between amino acids 1 and 153) functions efficiently in a variety of mammalian cell lines. The second domain (located between amino acids 369 and 485) functions preferentially in pancreatic beta cell lines. The latter domain shows a pattern of heptad repeats of leucine residues characteristics of "leucine zipper" transcription factors; site-directed mutagenesis of leucines within this repeat led to substantial reductions in activity. The selective properties of this activation domain may contribute to cell-specific transcription directed by the E2A gene.
E2A基因编码螺旋-环-螺旋（HLH）家族的转录因子，这些转录因子参与包括胰腺β细胞在内的多种细胞谱系中的细胞特异性转录调控。在本研究中，我们通过对E2A蛋白本身和Gal4-E2A融合蛋白进行缺失定位，表明该蛋白至少包含两个不同的激活域。一个域（位于氨基酸1至153之间）在多种哺乳动物细胞系中高效发挥作用。第二个域（位于氨基酸369至485之间）优先在胰腺β细胞系中发挥作用。后一个域显示出“亮氨酸拉链”转录因子特有的亮氨酸残基七肽重复模式；该重复序列中亮氨酸的定点诱变导致活性大幅降低。这个激活域的选择性特性可能有助于E2A基因指导的细胞特异性转录。
