Department of Molecular Genetics and Microbiology, Duke University Medical Center, Durham, NC 27710, United States.
Neurotoxicol Teratol. 2011 Nov-Dec;33(6):631-40. doi: 10.1016/j.ntt.2011.06.006. Epub 2011 Jul 13.
This is a review of research that supports a hypothesis regarding early restriction of gene expression in the vertebrate embryo. We hypothesize that vertebrate retinoic acid receptors (RARs for several vertebrates but rars for zebrafish) are part of an embryonic, epigenetic switch whose default position, at the time of fertilization is "OFF". This is due to the assemblage of a rar-corepressor-histone deacetylase complex on retinoic acid response elements (RAREs) in regulatory regions of a subset of genes. In addition, selective and precise allocation of retinoic acid during early development through the interaction of Phase I enzymes throws the switch "ON" in a predictable, developmental manner. We are proposing that this is a basic, early embryonic switch that can cause the initiation of cascades of gene expression that are responsible for at least some early, diversification of cell phenotypes. Dehydrogenases and a subset of cytochrome p450 genes (cyp26a1, cyp26b1, and cyp26c1) play the major role in providing the retinoic acid and limiting its access. We also suggest that this mechanism may be playing a significant role in the repression of genes in undifferentiated stem cells.
这是对支持脊椎动物胚胎中早期基因表达限制假说的研究的综述。我们假设脊椎动物视黄酸受体（几种脊椎动物的 RAR，但斑马鱼的 rars）是胚胎表观遗传开关的一部分，其默认位置在受精时为“关闭”。这是由于 rar-corepressor-组蛋白去乙酰化酶复合物在一组基因的调控区域的视黄酸反应元件（RARE）上组装。此外，通过 I 相酶的相互作用，在早期发育过程中对视黄酸进行选择性和精确的分配，以可预测的、发育的方式将开关“打开”。我们提出，这是一个基本的早期胚胎开关，可以引发基因表达级联的启动，这些级联至少负责一些早期细胞表型的多样化。脱氢酶和亚组细胞色素 P450 基因（cyp26a1、cyp26b1 和 cyp26c1）在提供视黄酸和限制其进入方面发挥主要作用。我们还认为，这种机制可能在未分化干细胞中基因的抑制中发挥重要作用。
