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Gene. 2019 Aug 30;711:143941. doi: 10.1016/j.gene.2019.143941. Epub 2019 Jun 23.

Analysis of the dynamic aberrant landscape of DNA methylation and gene expression during arsenic-induced cell transformation.

Author information

1
Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
2
Subdireccion de Investigación Básica, Instituto Nacional de Cancerología, Ciudad de México, Mexico.
3
DAMTP, Centre for Mathematical Sciences, University of Cambridge, Cambridge CB3 OWA, UK.
4
Laboratorio de Oncogenómica, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
5
Laboratorio de Biología Molecular, Servicio de Hematología, Hospital General de México "Dr. Eduardo Liceaga", Ciudad de México, Mexico.
6
Centro de Investigación en Salud "Dr. Jesús Kumate Rodríguez", Instituto Mexicano del Seguro Social, Mérida, Yucatán, Mexico; Cátedras CONACYT - Fundación IMSS AC, CONACYT, Ciudad de México, Mexico.
7
Laboratorio de Genómica de Enfermedades Psiquiátricas y Neurodegenerativas, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
8
Subdirección de Investigación Básica, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
9
Computational Genomics Consortium, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico.
10
Laboratorio de Inmunogenómica y Enfermedades Metabólicas, Instituto Nacional de Medicina Genómica, Ciudad de México, Mexico. Electronic address: fcenteno@inmegen.gob.mx.

Abstract

Inorganic arsenic is a well-known carcinogen associated with several types of cancer, but the mechanisms involved in arsenic-induced carcinogenesis are not fully understood. Recent evidence points to epigenetic dysregulation as an important mechanism in this process; however, the effects of epigenetic alterations in gene expression have not been explored in depth. Using microarray data and applying a multivariate clustering analysis in a Gaussian mixture model, we describe the alterations in DNA methylation around the promoter region and the impact on gene expression in HaCaT cells during the transformation process caused by chronic exposure to arsenic. Using this clustering approach, the genes were grouped according to their methylation and expression status in the epigenetic landscape, and the changes that occurred during the cellular transformation were identified adequately. Thus, we present a valuable method for identifying epigenomic dysregulation.

KEYWORDS:

Arsenic; Cell transformation; DNA methylation; Epigenetic regulation; Gene expression

PMID:
31242453
DOI:
10.1016/j.gene.2019.143941
[Indexed for MEDLINE]

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