Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer

Cervical cancer is the third female cancer most common worldwide. The carcinogenic process involves an alteration of the mechanisms associated with transcription. Several studies have reported an oncogenic role of the polycomb complex subunit, EZH2. However, the role of EZH2 in cervical cancer is un...

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Main Authors: Eric Genaro Salmerón-Bárcenas, Ana Elvira Zacapala-Gómez, Julio Ortiz-Ortiz, Francisco Israel Torres-Rojas, Pedro Antonio Avila-Lopez
Format: Article
Language:English
Published: IfADo - Leibniz Research Centre for Working Environment and Human Factors, Dortmund 2022-06-01
Series:EXCLI Journal : Experimental and Clinical Sciences
Subjects:
Online Access:https://www.excli.de/index.php/excli/article/view/5029
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author Eric Genaro Salmerón-Bárcenas
Ana Elvira Zacapala-Gómez
Julio Ortiz-Ortiz
Francisco Israel Torres-Rojas
Pedro Antonio Avila-Lopez
author_facet Eric Genaro Salmerón-Bárcenas
Ana Elvira Zacapala-Gómez
Julio Ortiz-Ortiz
Francisco Israel Torres-Rojas
Pedro Antonio Avila-Lopez
author_sort Eric Genaro Salmerón-Bárcenas
collection DOAJ
description Cervical cancer is the third female cancer most common worldwide. The carcinogenic process involves an alteration of the mechanisms associated with transcription. Several studies have reported an oncogenic role of the polycomb complex subunit, EZH2. However, the role of EZH2 in cervical cancer is unknown. Hence, the objective of this study was to determine the role of EZH2 in transcriptional regulation in cervical cancer. The EZH2 expression and the methylation status of its promoter were analyzed in The Cancer Genome Atlas. The EZH2 enrichment profile was analyzed using chromatin immunoprecipitation with massively parallel DNA sequencing data provided by ENCODE project. The chromatin compartments were identified in the 4D Nucleome Data Portal. The functional annotation was examined in Enrichr. We report that EZH2 expression is increased in cervical cancer which is associated with hypomethylation of its promoter. EZH2 is enriched at promoter and distal intergenic regions. We identified that EZH2 defines chromatin domains enriched with H3K27me3 within repressive compartments in the HeLa-S3 cell line. Additionally, high EZH2 expression is associated with the repression of the senescent phenotype in cervical cancer patients. Our results suggest the participation of EZH2 in the generation of domains with a silencer function in cervical cancer, which regulate the expression of genes associated with cellular senescence.
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spelling doaj.art-2efd59ef79bd4e47a8bc2138012af23f2023-04-20T13:18:52ZengIfADo - Leibniz Research Centre for Working Environment and Human Factors, DortmundEXCLI Journal : Experimental and Clinical Sciences1611-21562022-06-012185286810.17179/excli2022-50294468Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancerEric Genaro Salmerón-Bárcenas0https://orcid.org/0000-0002-1830-6724Ana Elvira Zacapala-Gómez1https://orcid.org/0000-0003-4935-6094Julio Ortiz-Ortiz2https://orcid.org/0000-0003-3082-4716Francisco Israel Torres-Rojas3https://orcid.org/0000-0003-4303-8677Pedro Antonio Avila-Lopez4https://orcid.org/0000-0002-0104-0771Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, MéxicoLaboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, MéxicoLaboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, MéxicoLaboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, MéxicoDepartment of Biochemistry and Molecular Genetics, Feinberg School of Medicine, Northwestern University, Chicago, Illinois 60611, USA. Telephone number: +52 55 6098 2694; E-mail: pedro.avilalopez@northwestern.eduCervical cancer is the third female cancer most common worldwide. The carcinogenic process involves an alteration of the mechanisms associated with transcription. Several studies have reported an oncogenic role of the polycomb complex subunit, EZH2. However, the role of EZH2 in cervical cancer is unknown. Hence, the objective of this study was to determine the role of EZH2 in transcriptional regulation in cervical cancer. The EZH2 expression and the methylation status of its promoter were analyzed in The Cancer Genome Atlas. The EZH2 enrichment profile was analyzed using chromatin immunoprecipitation with massively parallel DNA sequencing data provided by ENCODE project. The chromatin compartments were identified in the 4D Nucleome Data Portal. The functional annotation was examined in Enrichr. We report that EZH2 expression is increased in cervical cancer which is associated with hypomethylation of its promoter. EZH2 is enriched at promoter and distal intergenic regions. We identified that EZH2 defines chromatin domains enriched with H3K27me3 within repressive compartments in the HeLa-S3 cell line. Additionally, high EZH2 expression is associated with the repression of the senescent phenotype in cervical cancer patients. Our results suggest the participation of EZH2 in the generation of domains with a silencer function in cervical cancer, which regulate the expression of genes associated with cellular senescence.https://www.excli.de/index.php/excli/article/view/5029cervical cancerezh2-rich domainssilencerschromatin domainssenescence
spellingShingle Eric Genaro Salmerón-Bárcenas
Ana Elvira Zacapala-Gómez
Julio Ortiz-Ortiz
Francisco Israel Torres-Rojas
Pedro Antonio Avila-Lopez
Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
EXCLI Journal : Experimental and Clinical Sciences
cervical cancer
ezh2-rich domains
silencers
chromatin domains
senescence
title Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
title_full Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
title_fullStr Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
title_full_unstemmed Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
title_short Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer
title_sort integrated bioinformatics analysis reveals that ezh2 rich domains promote transcriptional repression in cervical cancer
topic cervical cancer
ezh2-rich domains
silencers
chromatin domains
senescence
url https://www.excli.de/index.php/excli/article/view/5029
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AT julioortizortiz integratedbioinformaticsanalysisrevealsthatezh2richdomainspromotetranscriptionalrepressionincervicalcancer
AT franciscoisraeltorresrojas integratedbioinformaticsanalysisrevealsthatezh2richdomainspromotetranscriptionalrepressionincervicalcancer
AT pedroantonioavilalopez integratedbioinformaticsanalysisrevealsthatezh2richdomainspromotetranscriptionalrepressionincervicalcancer