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Review
, 5 (6), e01951
eCollection

Mechanism of Methylation and Acetylation of High GDNF Transcription in Glioma Cells: A Review

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Review

Mechanism of Methylation and Acetylation of High GDNF Transcription in Glioma Cells: A Review

Lin Zhang et al. Heliyon.

Abstract

Gliomas are the most common primary malignant tumors in the central nervous system. High expression of glial cell line-derived neurotrophic factor (GDNF) is an important prerequisite for the initiation and development of gliomas. However, the underlying transcription mechanism is poorly understood. Epigenetic alterations are common and important hallmarks of various types of tumors, and lead to abnormal expression of genes. Several recent studies have suggested that epigenetic modifications contribute to increased GDNF transcription. Specifically, aberrant DNA methylation and histone acetylation in the promoter regions of GDNF are related to high GDNF transcription in glioma cells, where transcription factors have extremely important roles. Therefore, elucidating the importance and features of this underlying molecular mechanism will enhance our understanding and provide clues for the accurate diagnosis and efficacious treatment of gliomas. This review summarizes the latest thinking on the potential epigenetic mechanisms of high expression of GDNF in glioma cells focusing primarily on DNA methylation and histone acetylation.

Keywords: Cancer research; DNA methylation; GDNF; Genetics and molecular biology; Glioma; Histone acetylation; Oncology; Transcription factors.

Figures

Fig. 1
Fig. 1
Epigenetic mechanisms of high GDNF expression in glioma cells (adapted from Zhang et.al [54]). (A) Structure of human GDNF gene. Relative positions of the promoters, exons, and introns of human GDNF gene, and the status of methylation and histone H3K9 acetylation of GDNF promoters. -: down; +: up;/: unchanged. For example, “Methylation: -; +” denotes that, compared with normal tissue, the methylation level in low-grade glioma and high-grade glioma was decreased and increased, respectively. (B) Structure of GDNF promoter II. The promoter region II of GDNF contains two enhancers, two silencers, and multiple binding sites for transcription factors (AP-2, CREB, Egr-2, SP1). (C) Methylation- and acetylation-based mechanisms of high GDNF expression in glioma cells. The methylation or acetylation status in promoter II are more closely associated with high GDNF transcription. Abbreviation: GDNF, glial cell line-derived neurotrophic factor; AP-2, activator protein-2; CREB, cAMP-response element binding protein; Egr-2, early growth response protein 2; SP1, specificity protein 1.

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