Defining the Functional Targets of Cap’n’collar Transcription Factors NRF1, NRF2, and NRF3.
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ABSTRACT:
PROVIDER: PRJNA668112 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR12795553.fastq.gz | Fastqsanger.gz | |||
| SRR12795554.fastq.gz | Fastqsanger.gz | |||
| SRR12795555.fastq.gz | Fastqsanger.gz | |||
| SRR12795556.fastq.gz | Fastqsanger.gz | |||
| SRR12795557.fastq.gz | Fastqsanger.gz |
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Project description:The NRF transcription factors NRF1, NRF2, and NRF3, are a subset of Cap’n’collar transcriptional regulators which modulate the expression of genes harboring antioxidant-response element (ARE) sequences within their genomic loci. Despite the emerging physiological importance of NRF family members, the repertoire of their genetic targets remains incompletely defined. Here we use RNA-sequencing-based transcriptional profiling and quantitative proteomics to delineate the overlapping and differential genetic programs effected by the three NRF transcription factors. Comparing our data to recent profiling analyses, we create consensus target gene sets regulated by NRF1, NRF2, and NRF3, genetic programs which we determine to be differentially regulated in human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, essential information for future studies evaluating the role of NRF factors in normal physiology and disease.
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Project description:Transcription factor NRF1 (NFE2L1) has been reported to be activated by proteasome disfunction, although the target genes are poorly understood. We used microarrays to identify NRF3-regulated gene expression network related to proteostasis.
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Project description:The nuclear factor erythroid 2-related factor 2 (NRF2) transcription factor activates cytoprotective and metabolic gene expression in response to various electrophilic stressors. In disease, constitutive NRF2 activity promotes cancer progression while decreased NRF2 function contributes to neurodegenerative diseases. In contrast to the regulation of NRF2 protein stability in the cytoplasm, co-complexed proteins that govern NRF2 activity on chromatin are less clear. Using biotin proximity proteomics, we report networks for NRF2 and its family members NRF1, NRF3 and the NRF2 heterodimer MAFG. We found that the Parkinson’s disease zinc finger transcription factor ZNF746 (PARIS) physically associated with NRF2 and MAFG, resulting in suppression of NRF2-driven transcription. ZNF746 expression increased oxidative stress and apoptosis, phenotypes that were reversed by chemical and genetic hyperactivation of NRF2. This study presents a functionally annotated proximity network for NRF2 and suggests that ZNF746 overexpression in Parkinson’s disease directly inhibits NRF2-driven neuroprotection.
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