Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid receptor target genes in mouse embryonic fibroblasts
Genes involved in cell adhesion and signaling: a new repertoire of retinoic acid receptor target genes in mouse embryonic fibroblasts
复制标题
DOI：
10.1242/jcs.131946
复制
发表时间：
2014-02-01
影响因子：
4
通讯作者：
Rochette-Egly, Cecile
中科院分区：
文献类型：
--
作者：
Al Tanoury, Ziad;Piskunov, Aleksandr;Rochette-Egly, Cecile
核视黄酸（RA）受体（RAR α、β和γ）是调节参与细胞分化和增殖的一系列基因表达的配体依赖性转录因子。它们也是磷蛋白，我们以前已经证明了它们的磷酸化在转录活性中的重要性。在这里报道的研究中，我们通过比较野生型MEFs与缺乏三种RAR的MEFs，对小鼠胚胎成纤维细胞（MEFs）中受RAR调控的基因进行了全基因组分析。我们发现，在没有RA的情况下，RAR控制与细胞粘附相关的几个基因转录本的表达。因此，与WT细胞相比，敲除的MEFs不能粘附和在基质上扩散，并且它们显示出破坏的肌动蛋白丝网络。相反，在配体的存在下，RAR控制参与信号传导和RA代谢的其他基因的表达。利用在空白背景下表达RARa或RARc亚型（野生型或N末端磷酸化位点突变）的救援细胞系，我们发现RA靶基因的表达可以通过特定的单个RAR或RAR的组合来控制。根据基因的不同，RAR同种型。我们还选择了需要磷酸化受体的基因，以调节RA。我们的研究结果增加了由RAR调控的基因库，并突出了由RAR调控的转录程序的复杂性和多样性，这取决于基因。
Nuclear retinoic acid (RA) receptors (RARa, beta and gamma) are ligand-dependent transcription factors that regulate the expression of a battery of genes involved in cell differentiation and proliferation. They are also phosphoproteins and we previously showed the importance of their phosphorylation in their transcriptional activity. In the study reported here, we conducted a genome-wide analysis of the genes that are regulated by RARs in mouse embryonic fibroblasts (MEFs) by comparing wild-type MEFs to MEFs lacking the three RARs. We found that in the absence of RA, RARs control the expression of several gene transcripts associated with cell adhesion. Consequently the knockout MEFs are unable to adhere and to spread on substrates and they display a disrupted network of actin filaments, compared with the WT cells. In contrast, in the presence of the ligand, RARs control the expression of other genes involved in signaling and in RA metabolism. Taking advantage of rescue cell lines expressing the RARa or RARc subtypes (either wild-type or mutated at the N-terminal phosphorylation sites) in the null background, we found that the expression of RA-target genes can be controlled either by a specific single RAR or by a combination of RAR isotypes, depending on the gene. We also selected genes that require the phosphorylation of the receptors for their regulation by RA. Our results increase the repertoire of genes that are regulated by RARs and highlight the complexity and diversity of the transcriptional programs regulated by RARs, depending on the gene.