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Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells
(1) Background: Metal homeostasis is an important part of cellular programs and is disrupted when cells are exposed to carcinogenic heavy metals. Metal response is mediated by the metal response element transcription factor MTF-1. However, where MTF-1 binds and how that binding changes in response t...
Autores principales: | , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2023
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047149/ https://www.ncbi.nlm.nih.gov/pubmed/36980293 http://dx.doi.org/10.3390/cells12060953 |
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author | Wright, Gregory M. Black, Joshua C. |
author_facet | Wright, Gregory M. Black, Joshua C. |
author_sort | Wright, Gregory M. |
collection | PubMed |
description | (1) Background: Metal homeostasis is an important part of cellular programs and is disrupted when cells are exposed to carcinogenic heavy metals. Metal response is mediated by the metal response element transcription factor MTF-1. However, where MTF-1 binds and how that binding changes in response to heavy metals, such as cadmium, remains unknown. (2) Methods: To investigate the effects of prolonged cadmium exposure on the genomic distribution of MTF-1, we performed MTF-1 CUT&RUN, RNA-seq and ATAC-seq on control and cadmium-resistant cells. (3) Results: Changes in MTF-1 binding primarily occur distal to the transcription start sight. Newly occupied MTF-1 sites are enriched for FOS/JUN DNA binding motifs, while regions that lose MTF-1 binding in cadmium are enriched for the FOX transcription factor family member DNA binding sites. (4) Conclusions: Relocalization of MTF-1 to new genomic loci does not alter the accessibility of these locations. Our results support a model whereby MTF-1 is relocalized to accessible FOS/JUN-bound genomic locations in response to cadmium. |
format | Online Article Text |
id | pubmed-10047149 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2023 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-100471492023-03-29 Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells Wright, Gregory M. Black, Joshua C. Cells Article (1) Background: Metal homeostasis is an important part of cellular programs and is disrupted when cells are exposed to carcinogenic heavy metals. Metal response is mediated by the metal response element transcription factor MTF-1. However, where MTF-1 binds and how that binding changes in response to heavy metals, such as cadmium, remains unknown. (2) Methods: To investigate the effects of prolonged cadmium exposure on the genomic distribution of MTF-1, we performed MTF-1 CUT&RUN, RNA-seq and ATAC-seq on control and cadmium-resistant cells. (3) Results: Changes in MTF-1 binding primarily occur distal to the transcription start sight. Newly occupied MTF-1 sites are enriched for FOS/JUN DNA binding motifs, while regions that lose MTF-1 binding in cadmium are enriched for the FOX transcription factor family member DNA binding sites. (4) Conclusions: Relocalization of MTF-1 to new genomic loci does not alter the accessibility of these locations. Our results support a model whereby MTF-1 is relocalized to accessible FOS/JUN-bound genomic locations in response to cadmium. MDPI 2023-03-21 /pmc/articles/PMC10047149/ /pubmed/36980293 http://dx.doi.org/10.3390/cells12060953 Text en © 2023 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Wright, Gregory M. Black, Joshua C. Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title | Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title_full | Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title_fullStr | Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title_full_unstemmed | Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title_short | Genomic Redistribution of Metal-Response Transcription Factor-1 (MTF-1) in Cadmium Resistant Cells |
title_sort | genomic redistribution of metal-response transcription factor-1 (mtf-1) in cadmium resistant cells |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10047149/ https://www.ncbi.nlm.nih.gov/pubmed/36980293 http://dx.doi.org/10.3390/cells12060953 |
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