AN OCTAMER MOTIF CONTRIBUTES TO THE EXPRESSION OF THE RETINOIC ACID-REGULATED ZINC FINGER GENE REX-1 (ZFP-42) IN F9 TERATOCARCINOMA CELLS
AN OCTAMER MOTIF CONTRIBUTES TO THE EXPRESSION OF THE RETINOIC ACID-REGULATED ZINC FINGER GENE REX-1 (ZFP-42) IN F9 TERATOCARCINOMA CELLS
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DOI：
10.1128/mcb.13.5.2919
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发表时间：
1993-05-01
影响因子：
5.3
通讯作者：
GUDAS, LJ
中科院分区：
文献类型：
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作者：
HOSLER, BA;ROGERS, MB;GUDAS, LJ
锌指基因雷克斯-1（Zfp-42）的信使在未分化的小鼠F9畸胎瘤细胞和胚胎干细胞中表达。当通过添加视黄酸（RA）诱导F9细胞分化时，雷克斯-1的表达在转录水平上降低。我们已经分离了雷克斯-1基因（Zfp-42）的基因组DNA，表征了该基因的结构，并将该基因定位于小鼠8号染色体。已经鉴定了在F9细胞中有助于调节雷克斯-1启动子的启动子元件。F9干细胞中雷克斯-1启动子活性所需的区域含有八聚体基序（ATTTGCAT），其是DNA结合蛋白的POU结构域家族的八聚体转录因子成员的结合位点。包括该八聚体位点的雷克斯-1报告质粒在用RA处理的F9细胞中也表现出降低的表达。因此，八聚体基序是F9干细胞中雷克斯-1启动子活性所需的调节元件，并且该基序有助于RA对雷克斯-1基因转录的负调节。作为分离片段的体内相关性的初步确认，也含有八聚体位点的较大的雷克斯-1启动子片段能够促进细菌lacZ基因在桑椹胚阶段的小鼠胚胎中的表达。
The message for the zinc finger gene Rex-1 (Zfp-42) is expressed in undifferentiated murine F9 teratocarcinoma cells and embryonic stem cells. Expression of Rex-1 is reduced at the transcriptional level when F9 cells are induced by the addition of retinoic acid (RA) to differentiate. We have isolated genomic DNA for the Rex-1 gene (Zfp-42), characterized the gene's structure, and mapped the gene to mouse chromosome 8. Promoter elements contributing to the regulation of the Rex-1 promoter in F9 cells have been identified. A region required for Rex-1 promoter activity in F9 stem cells contains an octamer motif (ATTTGCAT) which is a binding site for octamer transcription factor members of the POU domain family of DNA-binding proteins. Rex-1 reporter plasmids including this octamer site also exhibited reduced expression in F9 cells treated with RA. Thus, the octamer motif is a regulatory element required for the activity of the Rex-1 promoter in F9 stem cells, and this motif contributes to the negative regulation by RA of the transcription of the Rex-1 gene. As an initial confirmation of the in vivo relevance of the isolated fragment, a larger Rex-1 promoter fragment, also containing the octamer site, was able to promote expression of the bacterial lacZ gene in mouse embryos at the morula stage.