Hepatocyte nuclear factor-1α, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription -: Implication for the developmental regulation of the sucrose-isomaltase gene
Hepatocyte nuclear factor-1α, GATA-4, and caudal related homeodomain protein Cdx2 interact functionally to modulate intestinal gene transcription -: Implication for the developmental regulation of the sucrose-isomaltase gene
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DOI：
10.1074/jbc.m204622200
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发表时间：
2002-08-30
影响因子：
4.8
通讯作者：
Traber, PG
中科院分区：
文献类型：
--
作者：
Boudreau, F;Rings, EHHM;Traber, PG
蔗糖酶-异麦芽糖酶（SI）是一种丝氨酸特异性基因，在小鼠哺乳-断奶过渡期的分化的小肠绒毛上皮中被诱导表达。我们以前已经确定了一个短的进化保守的SI启动子内的顺式作用元件。然而，相互作用的蛋白质的表达的性质和概况还没有得到充分的表征，在这个发展的过渡。在此，我们表明，肝细胞核因子-1 α（HNF-1 α），加塔-4，和尾部相关的同源结构域蛋白Cdx 2和Cdx 1是主要的转录因子从成年小鼠肠上皮细胞与SIF 3，加塔，和SIF 1元件的SI启动子。我们想研究HNF-1 α、加塔-4和Cdx 2是否能在SI基因表达的调控中协同作用。免疫定位实验表明，HNF-1 α是在哺乳小鼠的罕见上皮细胞中检测到的，并且在哺乳-断奶过渡期间在绒毛上皮细胞中表达逐渐增加。加塔-4蛋白仅在近端小肠的绒毛分化上皮细胞中表达，在回肠中表达降低，并且在结肠中变得不可检测。HNF-1 α、加塔-4和Cdx 2在体外和体内相互作用。这些因子在共转染实验中激活SI启动子活性，其中加塔-4需要HNF-1 α和Cdx 2两者的存在。这些发现暗示了HNF-1 α、Cdx 2和加塔-4在发育过程中对SI转录的时间和位置依赖性调控的组合作用。
Sucrase-isomaltase (SI), an intestine-specific gene, is induced in the differentiated small intestinal villous epithelium during the suckling-weaning transition in mice. We have previously identified cis-acting elements within a short evolutionarily conserved SI promoter. However, the nature and profile of expression of the interacting proteins have not been fully characterized during this developmental transition. Herein, we show that hepatocyte nuclear factor-1alpha (HNF-1alpha), GATA-4, and caudal related homeodomain proteins Cdx2 and Cdx1 are the primary transcription factors from the adult mouse intestinal epithelium to interact with the SIF3, GATA, and SIF1 elements of the SI promoter. We wanted to study whether HNF-1alpha, GATA-4, and Cdx2 can cooperate in the regulation of SI gene expression. Immunolocalization experiments revealed that HNF-1alpha is detected in rare epithelial cells of suckling mice and becomes progressively more expressed in the villous epithelial cells during the suckling-weaning transition. GATA-4 protein is expressed exclusively in villous differentiated epithelial cells of the proximal small intestine, decreases in expression in the ileum, and becomes undetectable in the colon. HNF-1alpha, GATA-4, and Cdx2 interact in vitro and in vivo. These factors activate SI promoter activity in cotransfection experiments where GATA-4 requires the presence of both HNF-1alpha and Cdx2. These findings imply a combinatory role of HNF-1alpha, Cdx2, and GATA-4 for the time- and position-dependent regulation of SI transcription during development.