Association between the promoter methylation of the TBX20 gene and tetralogy of fallot

Yang, Xiaofei; Kong, Qingyu; Li, Zhenghao; Xu, Min; Cai, Zhifeng; Zhao, Cuifen

doi:10.1080/14017431.2018.1499955

Cited by 12 publications

(10 citation statements)

References 31 publications

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“…Thus, during this period, the fetal troponin I1 isoform (Tnni1) is repressed by methylation, and, on the contrary, the postnatal Troponin I3 isoform (Tnni3) is activated through demethylation [ 127 , 129 ]. In the myocardium of patients with TF, high levels of methylation of the NKX2-5 and HAND1 promoters [ 130 ] and low levels of methylation of the TBX20 promoter are found in comparison with the control group, which is regarded as one of the factors in the pathogenesis of this CHD [ 130 , 131 , 132 ].…”

Section: Discussionmentioning

confidence: 99%

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

Sukhacheva

Серов

Nizyaeva

et al. 2022

Cells

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The myocardium of children with tetralogy of Fallot (TF) undergoes hemodynamic overload and hypoxemia immediately after birth. Comparative analysis of changes in the ploidy and morphology of the right ventricular cardiomyocytes in children with TF in the first years of life demonstrated their significant increase compared with the control group. In children with TF, there was a predominantly diffuse distribution of Connexin43-containing gap junctions over the cardiomyocytes sarcolemma, which redistributed into the intercalated discs as cardiomyocytes differentiation increased. The number of Ki67-positive cardiomyocytes varied greatly and amounted to 7.0–1025.5/106 cardiomyocytes and also were decreased with increased myocytes differentiation. Ultrastructural signs of immaturity and proliferative activity of cardiomyocytes in children with TF were demonstrated. The proportion of interstitial tissue did not differ significantly from the control group. The myocardium of children with TF under six months of age was most sensitive to hypoxemia, it was manifested by a delay in the intercalated discs and myofibril assembly and the appearance of ultrastructural signs of dystrophic changes in the cardiomyocytes. Thus, the acceleration of ontogenetic growth and differentiation of the cardiomyocytes, but not the reactivation of their proliferation, was an adaptation of the immature myocardium of children with TF to hemodynamic overload and hypoxemia.

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Section: Discussionmentioning

confidence: 99%

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

Sukhacheva

Серов

Nizyaeva

et al. 2022

Cells

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“…Recently, genes that belong to the Tbx1 ( TBX1 , TBX18 , and TBX20 ) and Tbx2 ( TBX2 , TBX5 ) subfamilies have been reported as transcriptional activators and gene repressors involved in the formation of chamber myocardium. These genes have also been associated with the development of CHDs, including atrial septal defect (ASD), ventricular septal defect (VSD), mitral valve disease (MVD) and tetralogy of Fallot (TOF), among others [ 5 , 8 , 9 , 10 , 11 ].…”

Section: Introductionmentioning

confidence: 99%

“…These epigenetic modifications play a key role in the pathophysiology of CHDs [ 14 , 15 , 16 , 17 ]. Furthermore, some studies have shown that an imbalance in the status of DNA methylation could change the expression of genes that participate in cardiogenesis [ 8 , 10 , 18 , 19 , 20 ].…”

Section: Introductionmentioning

confidence: 99%

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients

García-Flores

Rodrı́guez-Pérez

Borgonio-Cuadra

et al. 2022

Biology

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The TBX5 gene regulates morphological changes during heart development, and it has been associated with epigenetic abnormalities observed in congenital heart defects (CHD). The aim of this research was to evaluate the association between DNA methylation levels of the TBX5 gene promoter and congenital septal defects. DNA methylation levels of six CpG sites in the TBX5 gene promoter were evaluated using pyrosequencing analysis in 35 patients with congenital septal defects and 48 controls. Average methylation levels were higher in individuals with congenital septal defects than in the controls (p < 0.004). In five CpG sites, we also found higher methylation levels in patients than in the controls (p < 0.05). High methylation levels were associated with congenital septal defects (OR = 3.91; 95% CI = 1.02–14.8; p = 0.045). The analysis of Receiver Operating Characteristic (ROC) showed that the methylation levels of the TBX5 gene could be used as a risk marker for congenital septal defects (AUC = 0.68, 95% CI = 0.56–0.80; p = 0.004). Finally, an analysis of environmental factors indicated that maternal infections increased the risk (OR = 2.90; 95% CI = 1.01–8.33; p = 0.048) of congenital septal defects. Our data suggest that a high DNA methylation of the TBX5 gene could be associated with congenital septal defects.

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“…Abnormal gene expression during cardiac development leading to CHD may due to changes in the epigenetic landscape surrounding the genes’ regulatory regions, 2 and more complex causes of TOF may therefore be associated with epigenetic variation. A few studies have investigated the role of epigenetic modifications in TOF 1,13‐16 . We previously found that methylation abnormalities in multiple genes were involved in the pathogenesis of TOF 9,17‐19 and detected abnormal expression of some microRNAs (miRNAs) and significant changes in histone modification in injured heart tissues from TOF patients 20‐22 .…”

Section: Introductionmentioning

confidence: 99%

“…A few studies have investigated the role of epigenetic modifications in TOF. 1,[13][14][15][16] We previously found that methylation abnormalities in multiple genes were involved in the pathogenesis of TOF 9,[17][18][19] and detected abnormal expression of some microRNAs (miRNAs) and significant changes in histone modification in injured heart tissues from TOF patients. [20][21][22] As the largest class and most important component of non-coding RNAs, long non-coding RNAs (lncRNAs) of over 200 nucleotides are numerous in eukaryotes and function as transcriptional regulators in many cell processes and diseases.…”

Section: Introductionmentioning

confidence: 99%

Hypermethylation‐mediated down‐regulation of lncRNA TBX5‐AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression

Chen

Hao

et al. 2020

J Cellular Molecular Medi

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Tetralogy of Fallot (TOF) is the most common complex congenital heart disease (CHD) with uncertain cause. Although long non‐coding RNAs (lncRNAs) have been implicated in heart development and several CHDs, their role in TOF is not well understood. This study aimed to investigate how dysregulated lncRNAs contribute to TOF. Using Gene Expression Omnibus data mining, bioinformatics analysis and clinical heart tissue sample detecting, we identified a novel antisense lncRNA TBX5‐AS1:2 with unknown function that was significantly down‐regulated in injured cardiac tissues from TOF patients. LncRNA TBX5‐AS1:2 was mainly located in the nucleus of the human embryonic kidney 293 (HEK293T) cells and formed an RNA‐RNA double‐stranded structure in the overlapping region with its sense mRNA T‐box transcription factor 5 (TBX5), which is an important regulator in heart development. Knock‐down of lncRNA TBX5‐AS1:2 via promoter hypermethylation reduced TBX5 expression at both the mRNA and protein levels by affecting its mRNA stability through RNA‐RNA interaction. Moreover, lncRNA TBX5‐AS1:2 knock‐down inhibited the proliferation of HEK293T cells. In conclusion, these results indicated that lncRNA TBX5‐AS1:2 may be involved in TOF by affecting cell proliferation by targeting TBX5.

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Association between the promoter methylation of the TBX20 gene and tetralogy of fallot

Abstract: The downregulated methylation level at TBX20 promoter may be responsible for the elevated mRNA expression levels in patients with TOF. The abnormal methylation status of the TBX20 promoter may contribute to the pathogenesis of TOF.

Cited by 12 publications

References 31 publications

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

Accelerated Growth, Differentiation, and Ploidy with Reduced Proliferation of Right Ventricular Cardiomyocytes in Children with Congenital Heart Defect Tetralogy of Fallot

DNA Methylation Levels of the TBX5 Gene Promoter Are Associated with Congenital Septal Defects in Mexican Paediatric Patients

Hypermethylation‐mediated down‐regulation of lncRNA TBX5‐AS1:2 in Tetralogy of Fallot inhibits cell proliferation by reducing TBX5 expression

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