Histone H3K9 and H3K14 acetylation at the promoter of the LGALS9 gene is associated with mRNA levels in cervical cancer cells

LGALS9 基因启动子处的组蛋白 H3K9 和 H3K14 乙酰化与宫颈癌细胞中的 mRNA 水平相关

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作者:Erick Armenta-Castro, Tania Reyes-Vallejo, Daniel Máximo-Sánchez, Irma Herrera-Camacho, Gustavo López-López, Sandra Reyes-Carmona, Ileana Conde-Rodríguez, Ivonne Ramírez-Díaz, Adriana Aguilar-Lemarroy, Luis Felipe Jave-Suárez, Lorena Milflores-Flores, Gerardo Santos-Lopez, Julio Reyes-Leyva, Verónic

Abstract

Galectin-9 levels have been reported to be altered in several cancer types, but the mechanism that regulates the expression of Galectin-9 has not been clarified. Galectin-9 is encoded by the LGALS9 gene, which gives rise to eight mRNA variants. The aims of this study were: (a) to identify the mRNA variants of LGALS9, (b) to characterize CpG methylation and H3K9 and H3K14 histone acetylation at the promoter of the LGALS9 gene, and (c) to characterize the relationship between these modifications and LGALS9 expression level in cervical cancer cells. All mRNA variants were detected in HaCaT (nontumoural keratinocytes) and SiHa cells, and seven were observed in HeLa cells. The promoter region of LGALS9 contains eight CpG dinucleotides. No hypermethylation pattern related to low LGALS9 expression was identified in tumour cells. Chromatin immunoprecipitation analysis demonstrated higher acetylation of H3K9ac and H3K14ac in HaCaT cells, which was related to higher mRNA levels. The presence of the mRNA variants suggests that alternative splicing may regulate the expression of galectin-9 isoforms. The results of this study suggest that histone acetylation, but not promoter CpG methylation, may be involved in the transcriptional regulation of the LGALS9 gene.

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