Brown L, Baer R
Department of Microbiology, University of Texas Southwestern Medical Center, Dallas 75235.
Mol Cell Biol. 1994 Feb;14(2):1245-55. doi: 10.1128/mcb.14.2.1245-1255.1994.
HEN1 and HEN2 encode neuron-specific polypeptides that contain the basic helix-loop-helix (bHLH) motif, a protein dimerization and DNA-binding domain common to several known transcription factors. We now describe characteristics of the HEN1 gene product that are consistent with its postulated role as a transcription factor that functions during development of the mammalian nervous system. Thus, transcription of the HEN1 gene is activated upon the induction of neural differentiation in PC12 cells by nerve growth factor. HEN1 encodes a 20-kDa polypeptide (pp20HEN1) that is phosphorylated exclusively at serine residues and forms dimeric bHLH complexes either by self-association or by heterologous interaction with the E2A gene products (E12 or E47). The resultant HEN1/HEN1 homodimers and HEN1/E2A heterodimers bind DNA in a sequence-specific manner. Moreover, a binding site selection procedure revealed that HEN1-HEN1 homodimers preferentially recognize E-box motifs represented by an 18-bp consensus sequence (GGGNCG CAGCTGCGNCCC). The E-box half-site recognized by HEN1 polypeptides (GGGNCGCAG) is distinct from those of other known bHLH proteins, suggesting that HEN1 binds, an regulates the transcription of, a unique subset of target genes during neural development.
HEN1和HEN2编码神经元特异性多肽，这些多肽包含碱性螺旋-环-螺旋（bHLH）基序，这是几种已知转录因子共有的蛋白质二聚化和DNA结合结构域。我们现在描述HEN1基因产物的特征，这些特征与其作为在哺乳动物神经系统发育过程中起作用的转录因子的假定作用一致。因此，在神经生长因子诱导PC12细胞发生神经分化时，HEN1基因的转录被激活。HEN1编码一种20 kDa的多肽（pp20HEN1），该多肽仅在丝氨酸残基处磷酸化，并通过自我缔合或与E2A基因产物（E12或E47）的异源相互作用形成二聚体bHLH复合物。产生的HEN1/HEN1同二聚体和HEN1/E2A异二聚体以序列特异性方式结合DNA。此外，结合位点选择程序表明，HEN1-HEN1同二聚体优先识别由18个碱基对的共有序列（GGGNCG CAGCTGCGNCCC）代表的E-box基序。HEN1多肽识别的E-box半位点（GGGNCGCAG）与其他已知bHLH蛋白的不同，这表明HEN1在神经发育过程中结合并调节一组独特的靶基因的转录。
