Garrison Wendy D, Battle Michele A, Yang Chuhu, Kaestner Klaus H, Sladek Frances M, Duncan Stephen A
Department of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, Wisconsin 53326, USA.
Gastroenterology. 2006 Apr;130(4):1207-20. doi: 10.1053/j.gastro.2006.01.003.
BACKGROUND & AIMS: Hepatocyte nuclear factor 4 alpha (HNF4alpha) is a transcription factor that has been shown to be required for hepatocyte differentiation and development of the liver. It has also been implicated in regulating expression of genes that act in the epithelium of the lower gastrointestinal tract. This implied that HNF4alpha might be required for development of the gut.
Mouse embryos were generated in which Hnf4a was ablated in the epithelial cells of the fetal colon by using Cre-loxP technology. Embryos were examined by using a combination of histology, immunohistochemistry, DNA microarray, reverse-transcription polymerase chain reaction, electrophoretic mobility shift assays, and chromatin immunoprecipitation analyses to define the consequences of loss of HNF4alpha on colon development.
Embryos were recovered at E18.5 that lacked HNF4alpha in their colons. Although early stages of colonic development occurred, HNF4alpha-null colons failed to form normal crypts. In addition, goblet-cell maturation was perturbed and expression of an array of genes that encode proteins with diverse roles in colon function was disrupted. Several genes whose expression in the colon was dependent on HNF4alpha contained HNF4alpha-binding sites within putative transcriptional regulatory regions and a subset of these sites were occupied by HNF4alpha in vivo.
HNF4alpha is a transcription factor that is essential for development of the mammalian colon, regulates goblet-cell maturation, and is required for expression of genes that control normal colon function and epithelial cell differentiation.
肝细胞核因子4α（HNF4α）是一种转录因子，已被证明对肝细胞分化和肝脏发育至关重要。它还参与调节在下消化道上皮中起作用的基因的表达。这意味着HNF4α可能是肠道发育所必需的。
利用Cre-loxP技术构建了在胎儿结肠上皮细胞中Hnf4a基因被敲除的小鼠胚胎。通过组织学、免疫组织化学、DNA微阵列、逆转录聚合酶链反应、电泳迁移率变动分析和染色质免疫沉淀分析等方法对胚胎进行检测，以确定HNF4α缺失对结肠发育的影响。
在胚胎第18.5天回收的胚胎中，结肠缺乏HNF4α。虽然结肠发育的早期阶段发生了，但HNF4α基因敲除的结肠未能形成正常的隐窝。此外，杯状细胞成熟受到干扰，一系列在结肠功能中起不同作用的编码蛋白质的基因表达被破坏。结肠中表达依赖于HNF4α的几个基因在假定的转录调控区域内含有HNF4α结合位点，并且这些位点中的一部分在体内被HNF4α占据。
HNF4α是一种转录因子，对哺乳动物结肠发育至关重要，调节杯状细胞成熟，并且是控制正常结肠功能和上皮细胞分化的基因表达所必需的。
