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...

Full description

Bibliographic Details
Main Authors: Lara Ibrahim, Jaleh Mesgarzadeh, Ian Xu, Evan T. Powers, R. Luke Wiseman, Michael J. Bollong
Format: Article
Language:English
Published: MDPI AG 2020-10-01
Series:Antioxidants
Subjects:
Online Access:https://www.mdpi.com/2076-3921/9/10/1025
_version_ 1797550260156891136
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
work_keys_str_mv AT laraibrahim definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3
AT jalehmesgarzadeh definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3
AT ianxu definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3
AT evantpowers definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3
AT rlukewiseman definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3
AT michaeljbollong definingthefunctionaltargetsofcapncollartranscriptionfactorsnrf1nrf2andnrf3