Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3
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, th...
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MDPI AG
2020-10-01
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Series: | Antioxidants |
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Online Access: | https://www.mdpi.com/2076-3921/9/10/1025 |
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author | Lara Ibrahim Jaleh Mesgarzadeh Ian Xu Evan T. Powers R. Luke Wiseman Michael J. Bollong |
author_facet | Lara Ibrahim Jaleh Mesgarzadeh Ian Xu Evan T. Powers R. Luke Wiseman Michael J. Bollong |
author_sort | Lara Ibrahim |
collection | DOAJ |
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. We then create consensus target gene sets regulated by NRF1, NRF2, and NRF3 and define the integrity of these gene sets for probing NRF activity in mammalian cell culture and human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, providing a framework to understand the critical physiological importance of NRF transcription factors and to establish pharmacologic approaches for therapeutically activating these transcriptional programs in disease. |
first_indexed | 2024-03-10T15:26:47Z |
format | Article |
id | doaj.art-a68326cf2a6f41218b5aa6e3095085ad |
institution | Directory Open Access Journal |
issn | 2076-3921 |
language | English |
last_indexed | 2024-03-10T15:26:47Z |
publishDate | 2020-10-01 |
publisher | MDPI AG |
record_format | Article |
series | Antioxidants |
spelling | doaj.art-a68326cf2a6f41218b5aa6e3095085ad2023-11-20T18:01:03ZengMDPI AGAntioxidants2076-39212020-10-01910102510.3390/antiox9101025Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3Lara Ibrahim0Jaleh Mesgarzadeh1Ian Xu2Evan T. Powers3R. Luke Wiseman4Michael J. Bollong5Department of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Molecular Medicine, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USADepartment of Chemistry, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USAThe 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. We then create consensus target gene sets regulated by NRF1, NRF2, and NRF3 and define the integrity of these gene sets for probing NRF activity in mammalian cell culture and human tissues. Together, our data provide a quantitative assessment of how NRF family members sculpt proteomes and transcriptomes, providing a framework to understand the critical physiological importance of NRF transcription factors and to establish pharmacologic approaches for therapeutically activating these transcriptional programs in disease.https://www.mdpi.com/2076-3921/9/10/1025oxidative stress responseNRF transcription factorstranscriptomicsproteomicscellular pathway analysis |
spellingShingle | Lara Ibrahim Jaleh Mesgarzadeh Ian Xu Evan T. Powers R. Luke Wiseman Michael J. Bollong Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 Antioxidants oxidative stress response NRF transcription factors transcriptomics proteomics cellular pathway analysis |
title | Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 |
title_full | Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 |
title_fullStr | Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 |
title_full_unstemmed | Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 |
title_short | Defining the Functional Targets of Cap‘n’collar Transcription Factors NRF1, NRF2, and NRF3 |
title_sort | defining the functional targets of cap n collar transcription factors nrf1 nrf2 and nrf3 |
topic | oxidative stress response NRF transcription factors transcriptomics proteomics cellular pathway analysis |
url | https://www.mdpi.com/2076-3921/9/10/1025 |
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