Activation of the human PAX6 gene through the exon 1 enhancer by transcription factors SEF and Sp1.-猫眼课题宝

转录因子 SEF 和 Sp1 通过外显子 1 增强子激活人类 PAX6 基因。

DOI：

10.1093/nar/29.19.4070

发表时间：

2001

期刊：

Nucleic acids research

影响因子：

14.9

通讯作者：

中科院分区：

生物学2区

文献类型：

作者：

Zheng,JB;Zhou,YH;Maity,T;Liao,WS;Saunders,GF

PAX6 is a transcription factor that plays a major role in ocular morphogenesis. PAX6 is expressed in the eye, central nervous system and pancreas. Two alternative promoters, P0 and P1, which are differentially regulated during development, drivePAX6transcription. We identified a 57 bpcis-regulatory element in exon 1 of the humanPAX6gene exon 1 enhancer (EIE). EIE enhances P1-drivenPAX6expression. Three regions in E1E (E1E-1, E1E-2 and E1E-3) have sequence similarities with binding sites of transcription factors ARP-1, Isl-1 and SEF, respectively. As shown by electrophoretic mobility shift assays, E1E-3, but not E1E-1 or E1E-2, bound to proteins in nuclear extracts of human glioma cells and transcription factor SEF bound to E1E-3. As shown by transient transfection experiments, deletion or site-specific mutations in E1E-3 dramatically decreased P1 promoter activity. Mutations in E1E-2, however, did not affect function of the P1 promoter. Co-transfection of SEF andPAX6promoter–reporter constructs showed that SEF up-regulatesPAX6gene expression through the P1 promoter. Two Sp1 sites in the E1E region were also shown to be important by transient co-transfection assays. Data from immunoprecipitation and transient transfection assays demonstrated that SEF and Sp1 interactedin vitroand may act togetherin vivoto regulatePAX6expression.