The basic helix-loop-helix transcription factor BETA2/NeuroD is expressed in mammalian enteroendocrine cells and activates secretin gene expression
The basic helix-loop-helix transcription factor BETA2/NeuroD is expressed in mammalian enteroendocrine cells and activates secretin gene expression
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DOI：
10.1073/pnas.94.8.3560
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发表时间：
1997-04-15
影响因子：
11.1
通讯作者：
Leiter, AB
中科院分区：
文献类型：
--
作者：
Mutoh, H;Fung, BP;Leiter, AB
编码激素分泌蛋白的基因仅在发育过程中在肠内分泌S细胞和产生胰岛素的胰腺β细胞中表达。一个120 bp增强子指导大鼠分泌蛋白基因在表达分泌素的细胞中的细胞特异性表达。增强器包括一个电子框序列CAGCTG，这对于转录活性很重要。为了进一步表征E盒的作用，这是基本螺旋 - 环螺旋（BHLH）蛋白的共识结合位点，我们检查了与Synectin基因中与该元素相互作用的因素。结果表明，转录被最近分离的特异性BHLH蛋白BetA2激活，异二聚态二聚二聚在泛表达的BHLH蛋白，PAN 1和PAN 2，即E47和E12的啮齿动物同源物。反义实验进一步说明了β2对秘密蛋白的转录激活的重要性，该实验抑制了beta2在产生的细胞系中的beta2表达，从而抑制了大多数E盒依赖性转录的抑制。 β2在非内分泌细胞系中的表达赋予了在没有beta2的情况下以最小水平转录的表达分泌蛋白重生基因的能力。在小肠小肠中产生肠肠肠细胞的秘密蛋白显示出具有β2抗体的特异性免疫染色，从而证实了细胞系中的观察结果。因此，据我们所知，beta2是第一个转录因子，该因子明确激活了肠道激素基因的细胞类型特异性表达。
The gene encoding the hormone secretin is expressed only in enteroendocrine S cells and insulin-producing pancreatic beta cells during development. A 120-bp enhancer directs cell-specific expression of the rat secretin gene in secretin-expressing cells. The enhancer includes an E-box sequence, CAGCTG, which is important for transcriptional activity. To further characterize the role of the E box, a consensus binding site for basic helix-loop-helix (bHLH) proteins, we have examined factors that interact with this element in the secretin gene. The results suggest that transcription is activated by a recently isolated tissue specific bHLH protein, BETA2, heterodimerized to the ubiquitously expressed bHLH proteins, Pan 1 and Pan 2, the rodent homologues of E47 and E12. The importance of BETA2 for transcriptional activation of secretin is further illustrated by antisense experiments inhibiting BETA2 expression in secretin-producing cell lines, which resulted in the inhibition of most E box-dependent transcription. Expression of BETA2 in a nonendocrine cell line conferred the ability to express secretin-reporter genes that are transcribed at minimal levels in the absence of BETA2. Secretin producing enteroendocrine cells in the murine small intestine showed specific immunostaining with BETA2 antibodies, corroborating observations in cell lines. Thus BETA2 is to our knowledge the first transcription factor identified that specifically activates cell type-specific expression of an intestinal hormone gene.