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Multi-omics analysis identifies RFX7 targets involved in tumor suppression and neuronal processes
Katjana Schwab1, Luis Coronel1, Konstantin Riege1
1Computational Biology Group, Leibniz Institute on Aging-Fritz Lipmann Institute (FLI), Beutenbergstraße 11, 07745, Jena, Germany.
Abstract:
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.
Insights
The transcription factor RFX7 acts as a tumor suppressor, particularly in lymphoid cancers. New research reveals its broader gene network and role in neurological disorders, activated by p53 signaling.
Area of Science:
- Molecular Biology
- Oncology
- Neuroscience
Background:
- The transcription factor RFX7 is recurrently mutated in lymphoid neoplasms and is recognized as a tumor suppressor.
- Previous studies indicated potential roles for RFX7 in neurological and metabolic disorders, and its response to p53 signaling and cellular stress.
- RFX7 target genes are dysregulated across various cancer types, but its comprehensive network and function remain unclear.
Purpose of the Study:
- To elucidate the comprehensive target gene network of RFX7.
- To investigate the role of RFX7 in tumor suppression and neurological disorders.
- To understand the mechanistic link between RFX7, p53 signaling, and target gene activation.
Main Methods:
- Generation of RFX7 knock-out cell lines.
- Application of a multi-omics approach integrating transcriptome, cistrome, and proteome data.
- Analysis of RFX7 target genes and their regulation by p53 signaling.
Main Results:
- Identification of novel RFX7 target genes.
- Association of identified targets with RFX7's tumor suppressor functions.
- Evidence supporting RFX7's role in neurological disorders and its activation via p53 signaling.
Conclusions:
- RFX7 plays a significant role as a tumor suppressor, with implications beyond hematological malignancies.
- The study provides novel insights into RFX7's target gene network and its involvement in neurological conditions.
- RFX7 acts as a key mediator for activating specific genes in response to p53 signaling.
