Schwab Katjana, Coronel Luis, Riege Konstantin, Sacramento Erika K, Rahnis Norman, Häckes David, Cirri Emilio, Groth Marco, Hoffmann Steve, Fischer Martin
Computational Biology Group, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745, Jena, Germany.
Core Facility for Proteomics, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745, Jena, Germany.
Cell Death Discov. 2023 Mar 3;9(1):80. doi: 10.1038/s41420-023-01378-1.
Recurrently mutated in lymphoid neoplasms, the transcription factor RFX7 is emerging as a tumor suppressor. Previous reports suggested that RFX7 may also have a role in neurological and metabolic disorders. We recently reported that RFX7 responds to p53 signaling and cellular stress. Furthermore, we found RFX7 target genes to be dysregulated in numerous cancer types also beyond the hematological system. However, our understanding of RFX7's target gene network and its role in health and disease remains limited. Here, we generated RFX7 knock-out cells and employed a multi-omics approach integrating transcriptome, cistrome, and proteome data to obtain a more comprehensive picture of RFX7 targets. We identify novel target genes linked to RFX7's tumor suppressor function and underscoring its potential role in neurological disorders. Importantly, our data reveal RFX7 as a mechanistic link that enables the activation of these genes in response to p53 signaling.
转录因子RFX7在淋巴样肿瘤中经常发生突变,正逐渐成为一种肿瘤抑制因子。先前的报道表明,RFX7可能在神经和代谢紊乱中也发挥作用。我们最近报道,RFX7对p53信号和细胞应激有反应。此外,我们发现RFX7靶基因在许多癌症类型中也存在失调,不仅仅局限于血液系统。然而,我们对RFX7靶基因网络及其在健康和疾病中的作用的了解仍然有限。在这里,我们生成了RFX7敲除细胞,并采用多组学方法整合转录组、染色质组和蛋白质组数据,以更全面地了解RFX7的靶标。我们鉴定出与RFX7肿瘤抑制功能相关的新靶基因,并强调其在神经疾病中的潜在作用。重要的是,我们的数据揭示RFX7是一个机制性联系,能够响应p53信号激活这些基因。