Vincent Audrey, Van Seuningen Isabelle
Inserm, U837, Jean-Pierre Aubert Research Center, Team 5 Mucins, epithelial differentiation and carcinogenesis, Place de Verdun, 59045 Lille Cedex, France.
Differentiation. 2009 Sep-Oct;78(2-3):99-107. doi: 10.1016/j.diff.2009.07.002. Epub 2009 Jul 24.
Establishment and maintenance of epigenetic profiles are essential steps of development during which stem cells, despite identical genetic information, will acquire different and selective gene expression patterns, specific for their fate. This highly complex programming process involves mechanisms that are not yet completely understood although it has been established over the past few years that chromatin modifier enzymes (i.e. DNA and histone methyltransferases, histone deacetylases, histone demethylases, histone acetyltransferases) play essential roles in the establishment of transcriptional programs accompanying cell differentiation. Investigators in this field have been studying a wide variety of cell types including neural, muscular, mesenchymal and blood cells. This review will focus on epithelial cells of the digestive tract, intestinal stem cell niches being a model of choice to understand how epigenetic changes can drive nuclear programming and specific cell differentiation. Moreover, deregulation of epigenetic programming is frequently observed in human tumours and therefore, decoding these molecular mechanisms is essential to better understand both developmental and cancerous processes.
表观遗传图谱的建立和维持是发育过程中的关键步骤，在此期间，干细胞尽管具有相同的遗传信息，但会获得不同的、特定于其命运的选择性基因表达模式。这个高度复杂的编程过程涉及一些尚未完全理解的机制，尽管在过去几年中已经确定染色质修饰酶（即DNA和组蛋白甲基转移酶、组蛋白脱乙酰酶、组蛋白去甲基酶、组蛋白乙酰转移酶）在伴随细胞分化的转录程序建立中发挥着重要作用。该领域的研究人员一直在研究包括神经细胞、肌肉细胞、间充质细胞和血细胞在内的多种细胞类型。本综述将聚焦于消化道上皮细胞，肠道干细胞生态位是理解表观遗传变化如何驱动核编程和特定细胞分化的理想模型。此外，在人类肿瘤中经常观察到表观遗传编程失调，因此，解码这些分子机制对于更好地理解发育和癌变过程至关重要。
