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Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines

SIMPLE SUMMARY: RAD51 is a key enzyme involved in homologous recombination during DNA double-strand break repair. However, recent studies suggest that non-canonical roles of RAD51 may exist. The aim of our study was to assess regulatory roles of RAD51 by reanalyzing RAD51 ChIP-seq data in GM12878, H...

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Autores principales: Kang, Keunsoo, Choi, Yoonjung, Moon, Hyeonjin, You, Chaelin, Seo, Minjin, Kwon, Geunho, Yun, Jahyun, Beck, Boram, Kang, Kyuho
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196894/
https://www.ncbi.nlm.nih.gov/pubmed/34067336
http://dx.doi.org/10.3390/cancers13112547
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author Kang, Keunsoo
Choi, Yoonjung
Moon, Hyeonjin
You, Chaelin
Seo, Minjin
Kwon, Geunho
Yun, Jahyun
Beck, Boram
Kang, Kyuho
author_facet Kang, Keunsoo
Choi, Yoonjung
Moon, Hyeonjin
You, Chaelin
Seo, Minjin
Kwon, Geunho
Yun, Jahyun
Beck, Boram
Kang, Kyuho
author_sort Kang, Keunsoo
collection PubMed
description SIMPLE SUMMARY: RAD51 is a key enzyme involved in homologous recombination during DNA double-strand break repair. However, recent studies suggest that non-canonical roles of RAD51 may exist. The aim of our study was to assess regulatory roles of RAD51 by reanalyzing RAD51 ChIP-seq data in GM12878, HepG2, K562, and MCF-7 cell lines. We identified 5137, 2611, 7192, and 3498 RAD51-associated cis-regulatory elements in GM12878, HepG2, K562, and MCF-7 cell lines, respectively. Intriguingly, gene ontology analysis revealed that promoters of the autophagy pathway-related genes were most significantly occupied by RAD51 in all four cell lines, predicting a non-canonical role of RAD51 in regulating autophagy-related genes. ABSTRACT: RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins.
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spelling pubmed-81968942021-06-13 Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines Kang, Keunsoo Choi, Yoonjung Moon, Hyeonjin You, Chaelin Seo, Minjin Kwon, Geunho Yun, Jahyun Beck, Boram Kang, Kyuho Cancers (Basel) Article SIMPLE SUMMARY: RAD51 is a key enzyme involved in homologous recombination during DNA double-strand break repair. However, recent studies suggest that non-canonical roles of RAD51 may exist. The aim of our study was to assess regulatory roles of RAD51 by reanalyzing RAD51 ChIP-seq data in GM12878, HepG2, K562, and MCF-7 cell lines. We identified 5137, 2611, 7192, and 3498 RAD51-associated cis-regulatory elements in GM12878, HepG2, K562, and MCF-7 cell lines, respectively. Intriguingly, gene ontology analysis revealed that promoters of the autophagy pathway-related genes were most significantly occupied by RAD51 in all four cell lines, predicting a non-canonical role of RAD51 in regulating autophagy-related genes. ABSTRACT: RAD51 is a recombinase that plays a pivotal role in homologous recombination. Although the role of RAD51 in homologous recombination has been extensively studied, it is unclear whether RAD51 can be involved in gene regulation as a co-factor. In this study, we found evidence that RAD51 may contribute to the regulation of genes involved in the autophagy pathway with E-box proteins such as USF1, USF2, and/or MITF in GM12878, HepG2, K562, and MCF-7 cell lines. The canonical USF binding motif (CACGTG) was significantly identified at RAD51-bound cis-regulatory elements in all four cell lines. In addition, genome-wide USF1, USF2, and/or MITF-binding regions significantly coincided with the RAD51-associated cis-regulatory elements in the same cell line. Interestingly, the promoters of genes associated with the autophagy pathway, such as ATG3 and ATG5, were significantly occupied by RAD51 and regulated by RAD51 in HepG2 and MCF-7 cell lines. Taken together, these results unveiled a novel role of RAD51 and provided evidence that RAD51-associated cis-regulatory elements could possibly be involved in regulating autophagy-related genes with E-box binding proteins. MDPI 2021-05-22 /pmc/articles/PMC8196894/ /pubmed/34067336 http://dx.doi.org/10.3390/cancers13112547 Text en © 2021 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
Kang, Keunsoo
Choi, Yoonjung
Moon, Hyeonjin
You, Chaelin
Seo, Minjin
Kwon, Geunho
Yun, Jahyun
Beck, Boram
Kang, Kyuho
Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title_full Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title_fullStr Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title_full_unstemmed Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title_short Epigenomic Analysis of RAD51 ChIP-seq Data Reveals cis-regulatory Elements Associated with Autophagy in Cancer Cell Lines
title_sort epigenomic analysis of rad51 chip-seq data reveals cis-regulatory elements associated with autophagy in cancer cell lines
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8196894/
https://www.ncbi.nlm.nih.gov/pubmed/34067336
http://dx.doi.org/10.3390/cancers13112547
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