Transcriptional and Translational Regulation of β-Cell Differentiation Factor Nkx6.1*-猫眼课题宝

β 细胞分化因子 Nkx6.1* 的转录和翻译调节

DOI：

发表时间：

2000

期刊：

Journal of Biological Chemistry

影响因子：

4.8

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

H. Watada;R. Mirmira;J. Leung;M. German

In the mature pancreas, the homeodomain transcription factor Nkx6.1 is uniquely restricted to β-cells. Nkx6.1 also is expressed in developing β-cells and plays an essential role in their differentiation. Among cell lines, both β- and α-cell lines express nkx6.1 mRNA; but no protein can be detected in the α-cell lines, suggesting that post-transcriptional regulation contributes to the restriction of Nkx6.1 to β-cells. To investigate the regulator of Nkx6.1 expression, we outlined the structure of the mouse nkx6.1 gene, and we identified regions that direct cell type-specific expression. Thenkx6.1 gene has a long 5′-untranslated region (5′-UTR) downstream of a cluster of transcription start sites.nkx6.1 gene sequences from −5.6 to +1.0 kilobase pairs have specific promoter activity in β-cell lines but not in NIH3T3 cells. This activity is dependent on sequences located at about −800 base pairs and on the 5′-UTR. Electrophoretic mobility shift assays demonstrate that homeodomain transcription factors PDX1 and Nkx2.2 can bind to the sequence element located at −800 base pairs. In addition, dicistronic assays establish that the 5′-UTR region functions as a potent internal ribosomal entry site, providing cell type-specific regulation of translation. These data demonstrate that complex regulation of both Nkx6.1 transcription and translation provides the specificity of expression required during pancreas development.