CpG site hypomethylation at ETS1‑binding region regulates DLK1 expression in Chinese patients with Tetralogy of Fallot

Tian, Guixiang; He, Lili; Gu, Rong; Sun, Jingwei; Chen, Wei-Cheng; Qian, Yanyan; Ma, Xiaojing; Yan, Weili; Zhenshan, Zhao; Xu, Ziqing; Suo, Mei-Jiao; Wei, Sheng; Huang, Guoying

doi:10.3892/mmr.2022.12609

Cited by 2 publications

(3 citation statements)

References 36 publications

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“…Consistently, blood leucocytes and right atrial tissues displayed distinct DNA methylation profiles in patients that underwent coronary artery bypass surgery [124]. In TOF RVOT or RV myocardium, an impaired DNA methylation landscape affected ETS1, RXR, and SP1 binding sites and contributed to decreased DLK1, NOTCH4, and TBX20 gene expression [125][126][127][128][129][130]. Notably, hypomethylating drugs influenced the interaction between RXR, ETS1, and their respective binding sites in vitro [126,130].…”

Section: Dna Methylationmentioning

confidence: 90%

“…In TOF RVOT or RV myocardium, an impaired DNA methylation landscape affected ETS1, RXR, and SP1 binding sites and contributed to decreased DLK1, NOTCH4, and TBX20 gene expression [125][126][127][128][129][130]. Notably, hypomethylating drugs influenced the interaction between RXR, ETS1, and their respective binding sites in vitro [126,130]. Additionally, the impaired DNA methylation of NKX2-5, EGFR, EVC2, TBX5, CFC1B, RXRa, VANGL2, TBX20, NR2F2, NOTCH4, and DLK1 correlated or was associated with the impaired expression of their respective transcripts [126][127][128][129][130][131][132][133][134].…”

Section: Dna Methylationmentioning

confidence: 99%

“…Notably, hypomethylating drugs influenced the interaction between RXR, ETS1, and their respective binding sites in vitro [126,130]. Additionally, the impaired DNA methylation of NKX2-5, EGFR, EVC2, TBX5, CFC1B, RXRa, VANGL2, TBX20, NR2F2, NOTCH4, and DLK1 correlated or was associated with the impaired expression of their respective transcripts [126][127][128][129][130][131][132][133][134]. Interestingly, the DNA methylation of TBX20 (affected in TOF patients) was unaffected in the RVs and blood of DCM patients, suggesting a potential specificity of DNA methylation changes for the pathologic condition affecting the RV [135,136].…”

Section: Dna Methylationmentioning

confidence: 99%

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Right Ventricle and Epigenetics: A Systematic Review

Toro,

Jutras-Beaudoin,

Boucherat

et al. 2023

Cells

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There is an increasing recognition of the crucial role of the right ventricle (RV) in determining the functional status and prognosis in multiple conditions. In the past decade, the epigenetic regulation (DNA methylation, histone modification, and non-coding RNAs) of gene expression has been raised as a critical determinant of RV development, RV physiological function, and RV pathological dysfunction. We thus aimed to perform an up-to-date review of the literature, gathering knowledge on the epigenetic modifications associated with RV function/dysfunction. Therefore, we conducted a systematic review of studies assessing the contribution of epigenetic modifications to RV development and/or the progression of RV dysfunction regardless of the causal pathology. English literature published on PubMed, between the inception of the study and 1 January 2023, was evaluated. Two authors independently evaluated whether studies met eligibility criteria before study results were extracted. Amongst the 817 studies screened, 109 studies were included in this review, including 69 that used human samples (e.g., RV myocardium, blood). While 37 proposed an epigenetic-based therapeutic intervention to improve RV function, none involved a clinical trial and 70 are descriptive. Surprisingly, we observed a substantial discrepancy between studies investigating the expression (up or down) and/or the contribution of the same epigenetic modifications on RV function or development. This exhaustive review of the literature summarizes the relevant epigenetic studies focusing on RV in human or preclinical setting.

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