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

Authors

  • Eric Genaro Salmerón-Bárcenas Departamento de Biomedicina Molecular, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Ciudad de México 07360, México https://orcid.org/0000-0002-1830-6724
  • Ana Elvira Zacapala-Gómez Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, México https://orcid.org/0000-0003-4935-6094
  • Julio Ortiz-Ortiz Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, México https://orcid.org/0000-0003-3082-4716
  • Francisco Israel Torres-Rojas Laboratorio de Biomedicina Molecular, Facultad de Ciencias Químico Biológicas, Universidad Autónoma de Guerrero, Chilpancingo 39070, Guerrero, México https://orcid.org/0000-0003-4303-8677
  • Pedro Antonio Avila-Lopez Department 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.edu https://orcid.org/0000-0002-0104-0771

DOI:

https://doi.org/10.17179/excli2022-5029

Keywords:

cervical cancer, EZH2-rich domains, silencers, chromatin domains, senescence

Abstract

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.

Downloads

Additional Files

Published

2022-06-23

How to Cite

Salmerón-Bárcenas, E. G., Zacapala-Gómez, A. E., Ortiz-Ortiz, J., Torres-Rojas, F. I., & Avila-Lopez, P. A. (2022). Integrated bioinformatics analysis reveals that EZH2-rich domains promote transcriptional repression in cervical cancer. EXCLI Journal, 21, 852–868. https://doi.org/10.17179/excli2022-5029

Issue

Section

Original articles

Categories