Instituto de Investigaciones Biomédicas, Alberto Sols Consejo Superior de Investigaciones Científicas, Universidad Autónoma de Madrid, Madrid, Spain.
Dev Dyn. 2010 Mar;239(3):980-6. doi: 10.1002/dvdy.22217.
While much is known about Groucho corepressors in Drosophila development, less is known about Grg homologs in mammalian embryogenesis. The transcription factors FoxA1 and FoxA2 are redundantly necessary for liver-inductive competence of the endoderm, and recently we found that FoxA factors bind Grg3, recruit the corepressor to FoxA target genes, and cause transcriptional repression, when Grg3 is ectopically expressed in adult liver cell lines that express little or no endogenous Grg. Unexpectedly, we now find that Grg1 and Grg3 mRNAs are co-expressed with FoxA factors in the foregut endoderm, prior to liver differentiation, though only Grg3 protein is expressed there. Grg3 mRNA and protein are extinguished at the onset of liver differentiation. Lentiviral delivery of Grg3 to explants of foregut endoderm suppresses liver gene induction. We suggest that Grg expression in the endoderm helps suppress the liver program and find that endodermal competence involves a balance between activators and corepressors.
虽然人们对果蝇发育过程中的 Groucho 核心抑制物了解较多，但对哺乳动物胚胎发生过程中的 Grg 同源物了解较少。转录因子 FoxA1 和 FoxA2 对于内胚层的肝诱导能力是冗余必需的，最近我们发现 FoxA 因子与 Grg3 结合，将核心抑制物募集到 FoxA 靶基因上，并导致转录抑制，当 Grg3 在表达很少或不表达内源性 Grg3 的成年肝细胞系中异位表达时。出乎意料的是，我们现在发现 Grg1 和 Grg3mRNA 在肝分化之前与 FoxA 因子在前肠内胚层中共表达，尽管那里只表达 Grg3 蛋白。Grg3mRNA 和蛋白在肝分化开始时被熄灭。慢病毒向前肠内胚层外植体传递 Grg3 可抑制肝基因的诱导。我们认为内胚层中的 Grg 表达有助于抑制肝程序，并且发现内胚层的能力涉及激活剂和核心抑制物之间的平衡。
