A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation.
A LncRNA-MAF:MAFB transcription factor network regulates epidermal differentiation.
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DOI：
10.1016/j.devcel.2015.01.028
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发表时间：
2015-03-23
影响因子：
11.8
通讯作者：
Khavari, Paul A.
中科院分区：
文献类型：
--
作者：
Lopez-Pajares, Vanessa;Qu, Kun;Zhang, Jiajing;Webster, Dan E.;Barajas, Brook C.;Siprashvili, Zurab;Zarnegar, Brian J.;Boxer, Lisa D.;Rios, Eon J.;Tao, Shiying;Kretz, Markus;Khavari, Paul A.
祖细胞的分化需要基因组表达的重塑；然而，在许多组织中，如表皮，重塑的基因和控制它们的转录因子(TF)的谱还没有完全确定。我们在分化的表皮再生过程中进行了动态转录组分析，确定了在祖细胞(594个基因)、早期(159个基因)和晚期分化(387个基因)中富含的基因集。1,046个TF的模块图谱表明MAF和MAFB对于祖细胞的分化是必要的和充分的。MAF：MAFB调控了393个在这种情况下改变的基因。综合分析确定ANCR和TINCR lncRNAs是MAF：MAFB上游必需的调控因子。CHIP-SEQ分析表明MAF：MAFB与已知的表皮分化因子基因结合，这些基因的表达受到调控，包括GRHL3、ZNF750、KLF4和PRDM1。在MAF：MAFB缺失的情况下，这些转录因子均挽救了特定MAF：MAFB靶基因亚组的表达，表明它们作用于MAF：MAFB的下游。因此，lncRNA-Tf网络对表皮分化是必不可少的。
Progenitor differentiation requires remodeling of genomic expression; however, in many tissues, such as epidermis, the spectrum of remodeled genes and the transcription factors (TFs) that control them are not fully defined. We performed kinetic transcriptome analysis during regeneration of differentiated epidermis and identified gene sets enriched in progenitors (594 genes), in early (159 genes), and in late differentiation (387 genes). Module mapping of 1,046 TFs identified MAF and MAFB as necessary and sufficient for progenitor differentiation. MAF:MAFB regulated 393 genes altered in this setting. Integrative analysis identified ANCR and TINCR lncRNAs as essential upstream MAF:MAFB regulators. ChIP-seq analysis demonstrated MAF:MAFB binding to known epidermal differentiation TF genes whose expression they controlled, including GRHL3, ZNF750, KLF4, and PRDM1. Each of these TFs rescued expression of specific MAF:MAFB target gene subsets in the setting of MAF:MAFB loss, indicating they act downstream of MAF:MAFB. A lncRNA-TF network is thus essential for epidermal differentiation.
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