Centre for Skin Sciences, University of Bradford, Bradford, UK.
J Invest Dermatol. 2012 Nov;132(11):2505-21. doi: 10.1038/jid.2012.182. Epub 2012 Jul 5.
The nucleus is a complex and highly compartmentalized organelle, which undergoes major organization changes during cell differentiation, allowing cells to become specialized and fulfill their functions. During terminal differentiation of the epidermal keratinocytes, the nucleus undergoes a programmed transformation from active status, associated with execution of the genetic programs of cornification and epidermal barrier formation, to a fully inactive condition and becomes a part of the keratinized cells of the cornified layer. Tremendous progress achieved within the past two decades in understanding the biology of the nucleus and epigenetic mechanisms controlling gene expression allowed defining several levels in the regulation of cell differentiation-associated gene expression programs, including an accessibility of the gene regulatory regions to DNA-protein interactions, covalent DNA and histone modifications, and ATP-dependent chromatin remodeling, as well as higher-order chromatin remodeling and nuclear compartmentalization of the genes and transcription machinery. Here, we integrate our current knowledge of the mechanisms controlling gene expression during terminal keratinocyte differentiation with distinct levels of chromatin organization and remodeling. We also propose directions to further explore the role of epigenetic mechanisms and their interactions with other regulatory systems in the control of keratinocyte differentiation in normal and diseased skin.
核是一个复杂而高度分隔的细胞器，在细胞分化过程中经历主要的组织变化，使细胞能够特化并发挥其功能。在表皮角质形成细胞的终末分化过程中，核经历从活跃状态到完全不活跃状态的程序性转化，与角质化和表皮屏障形成的遗传程序的执行相关联，并成为角化细胞的一部分角质层。在过去的二十年中，在理解核的生物学和控制基因表达的表观遗传机制方面取得了巨大进展，这使得我们能够定义细胞分化相关基因表达程序调控的几个水平，包括基因调控区域对 DNA-蛋白质相互作用、共价 DNA 和组蛋白修饰以及 ATP 依赖性染色质重塑的可及性，以及更高级别的染色质重塑和基因以及转录机制的核分隔。在这里，我们将控制终末角质形成细胞分化过程中基因表达的机制与染色质组织和重塑的不同水平进行整合。我们还提出了进一步探索表观遗传机制及其与其他调控系统相互作用在正常和患病皮肤中控制角质形成细胞分化的作用的方向。
