Labott Andrew T, Lopez-Pajares Vanessa
a Program in Epithelial Biology, Stanford University , Stanford , CA , USA.
Cell Cycle. 2016 Jun 2;15(11):1405-9. doi: 10.1080/15384101.2016.1172148. Epub 2016 Apr 20.
Numerous regulatory factors in epidermal differentiation and their role in regulating different cell states have been identified in recent years. However, the genetic interactions between these regulators over the dynamic course of differentiation have not been studied. In this Extra-View article, we review recent work by Lopez-Pajares et al. that explores a new regulatory network in epidermal differentiation. They analyze the changing transcriptome throughout epidermal regeneration to identify 3 separate gene sets enriched in the progenitor, early and late differentiation states. Using expression module mapping, MAF along with MAFB, are identified as transcription factors essential for epidermal differentiation. Through double knock-down of MAF:MAFB using siRNA and CRISPR/Cas9-mediated knockout, epidermal differentiation was shown to be impaired both in-vitro and in-vivo, confirming MAF:MAFB's role to activate genes that drive differentiation. Lopez-Pajares and collaborators integrated 42 published regulator gene sets and the MAF:MAFB gene set into the dynamic differentiation gene expression landscape and found that lncRNAs TINCR and ANCR act as upstream regulators of MAF:MAFB. Furthermore, ChIP-seq analysis of MAF:MAFB identified key transcription factor genes linked to epidermal differentiation as downstream effectors. Combined, these findings illustrate a dynamically regulated network with MAF:MAFB as a crucial link for progenitor gene repression and differentiation gene activation.
近年来，人们已经确定了许多表皮分化中的调控因子及其在调节不同细胞状态中的作用。然而，尚未研究这些调控因子在分化动态过程中的基因相互作用。在这篇观点延伸文章中，我们回顾了洛佩斯 - 帕哈雷斯等人最近的工作，他们探索了表皮分化中的一个新调控网络。他们分析了整个表皮再生过程中不断变化的转录组，以确定在祖细胞、早期和晚期分化状态中富集的3个独立基因集。通过表达模块映射，MAF以及MAFB被确定为表皮分化所必需的转录因子。使用小干扰RNA（siRNA）和CRISPR/Cas9介导的基因敲除对MAF:MAFB进行双敲除，结果表明表皮分化在体外和体内均受到损害，证实了MAF:MAFB激活驱动分化基因的作用。洛佩斯 - 帕哈雷斯及其合作者将42个已发表的调控因子基因集和MAF:MAFB基因集整合到动态分化基因表达图谱中，发现长链非编码RNA（lncRNA）TINCR和ANCR作为MAF:MAFB的上游调控因子。此外，对MAF:MAFB的染色质免疫沉淀测序（ChIP-seq）分析确定了与表皮分化相关的关键转录因子基因作为下游效应器。综合这些发现表明，存在一个以MAF:MAFB为祖细胞基因抑制和分化基因激活关键环节的动态调控网络。
