Hypomethylation and decreased expression of <i>BRG1</i> in the myocardium of patients with congenital heart disease

Qian, Yanyan; Xiao, Deyong; Chen, Hongbo; Hao, Lili; Ma, Xiaojing; Huang, Guoying; Ma, Ding; Wang, Huijun

doi:10.1002/bdr2.1053

Cited by 16 publications

(11 citation statements)

References 59 publications

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“…The current study represents a genome-wide methylation analysis of relatively complicated cardiac defects. Previous DNA methylation studies were limited to analyses of methylation status in some congenital heart defect candidate genes (10,11,(21)(22)(23), and were insufficient to reveal information for DNA methylation on a global scale. One previous study conducted a genome-wide DNA methylation study (24) and found more hypermethylated than hypomethylated DMRs in myocardial samples from pediatric patients with CHDs compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, in heart tissue samples from patients 1-48 months in age, decreased whole-genome methylation levels, implied by analyzing long interspersed nucleotide element (LINE)1 methylation status, was associated with increased risk of tetralogy of fallot (TOF) ( 9 ). Changes in DNA methylation at the promoter and intron regions of several heart development-related genes, including NK2 homeobox 5, GATA binding protein 4, heart and neural crest derivatives expressed 1, and SWI/SNF-related matrix associated actin-dependent regulator of chromatin subfamily a member 4, and their association with the expression of these genes, have also been reported in the myocardium of children with ventricular septal defect (VSD), TOF, and double-chambered right ventricle ( 10 , 11 ). However, limited studies have examined DNA methylation during the fetal period, a key stage when cardiac structures are forming.…”

Section: Introductionmentioning

confidence: 99%

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Genome‑wide methylation analysis reveals differentially methylated CpG sites and altered expression of heart development‑associated genes in fetuses with cardiac defects

et al. 2021

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DNA methylation, as an epigenetic mechanism, has a vital role in heart development. An increasing number of studies have investigated aberrant DNA methylation in pediatric or adult heart samples from patients with congenital heart defects (CHD). Placenta tissue, umbilical cord blood, or newborn blood have also been used to detect DNA methylation biomarkers for CHD. However, few studies have compared the methylation levels in fetal heart tissue with cardiac defects with that in normal controls. The present study conducted an integrative whole-genome and CpG site-specific DNA methylation analysis of fetal heart samples from 17 isolated cardiac defect cases, 14 non-isolated cardiac defect cases, and 22 controls with normal hearts, using methylated DNA immunoprecipitation microarray and MassARRAY EpiTYPER assays. Expression of genes adjacent to differentially methylated regions (DMRs) was measured by RT-qPCR and western blot analysis. The results revealed that fetuses with cardiac defects presented global hypomethylation. Genomic analysis of DMRs revealed that a proportion of DMRs were located in exons (12.4%), distal intergenic regions (11.14%), and introns (8.97%). Only 55.7% of DMRs were observed at promoter regions. Functional enrichment analysis for genes adjacent to these DMRs revealed that hypomethylated genes were involved in embryonic heart tube morphogenesis and immune-related regulation functions. Intergenic hypermethylation of EGFR and solute carrier family 19 member 1 (SLC19A1), and intragenic hypomethylation of NOTCH1 were validated in fetal heart tissues with cardiac defects. Only SLC19A1 expression was significantly decreased at the mRNA level, while EGFR, NOTCH1, and SLC19A1 expression were all significantly decreased at the protein level. In conclusion, the present study demonstrated that fetal cardiac defects may be associated with alterations in regional and single CpG site methylation outside of promoter regions, resulting in differentiated expression of corresponding genes associated with heart development. These results present new insights into the epigenetic mechanisms underlying abnormal heart development.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genome‑wide methylation analysis reveals differentially methylated CpG sites and altered expression of heart development‑associated genes in fetuses with cardiac defects

et al. 2021

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“…Interestingly, the down-regulation of BRG1 gene expression at birth was also observed in normal human hearts. However, unlike in adult mouse hearts where the BRG1 was undetectable in cardiomyocytes, it remains detectable in human adult cardiomyocytes, suggesting the other mechanisms may be present in regulating the switch of fetal and adult MHC in humans (50). Nevertheless, in hypertrophic and failing hearts, the subunits of BAF complexes and its binding partners, HDACs and PARPs, were increased and the expression of fetal MHC was up-regulated, whereas the adult MHC was decreased (46).…”

Section: Atp-dependent Chromatin Conformation Remodeling and Hfmentioning

confidence: 95%

Epigenetics in Cardiac Hypertrophy and Heart Failure

Liu

Tang

2019

JACC: Basic to Translational Science

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HighlightsEpigenetic mechanisms associated with the pathological process of cardiac hypertrophy and failure include DNA methylation, post-modification of histones, ATP-dependent chromatin conformation and remodeling, and non-coding RNAs.Systemic- and cardiac-epigenetic mechanisms may both influence the disease processes of cardiac hypertrophy and failure.Identifying vital epigenetic machinery in cardiac diseases may facilitate developing personalized therapy for HF.

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“…Studies have shown that there are hypermethylation of myocardial-related genes in myocardial tissues of CHD, which is closely related to gene downregulation [4,5]. In patients with CHD, decreased transcriptional activity of CITE2, ZIC3, NR2F2 and BRG1 is associated with abnormal methylation [6][7][8][9].…”

Section: Introductionmentioning

confidence: 99%

DNA methylation abnormalities of imprinted genes in congenital heart disease: A pilot study

Chang

Wang

Xin

et al. 2020

Preprint

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Background: Congenital heart disease (CHD) is resulted from the interaction of genetic aberration and environmental factors. Imprinted genes, which are regulated by epigenetic modifications, are essential for the normal embryonic development. However, the role of imprinted genes in the etiology of CHD remains unclear. Results: We investigated the alterations of imprinted gene germline differential methylation regions (gDMRs) methylation in patients with CHD. Eighteen imprinted genes that are known to affect early embryonic development were selected and the methylation modification genes were detected by massarray in 27 CHD children and 28 healthy children. Altered gDMR methylation level of 8 imprinted genes was found, including 2 imprinted genes with hypermethylation of GRB10 and MEST and 6 genes with hypomethylation of PEG10, NAP1L5, INPP5F, PLAGL1, NESP and MEG3. Stratified analysis showed that the methylation degree of imprinted genes was different in different types of CHD. Risk analysis showed that 6 imprinted genes, except MEST and NAP1L5, within a specific methylation level range were the risk factors for CHDConclusion: Altered methylation of imprinted genes is associated with CHD and varies in different types of CHD. Further experiments are warranted to identify the methylation characteristics of imprinted genes in different types of CHD and clarify the etiologies of imprinted genes in CHD.

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Hypomethylation and decreased expression of BRG1 in the myocardium of patients with congenital heart disease

Cited by 16 publications

References 59 publications

Genome‑wide methylation analysis reveals differentially methylated CpG sites and altered expression of heart development‑associated genes in fetuses with cardiac defects

Genome‑wide methylation analysis reveals differentially methylated CpG sites and altered expression of heart development‑associated genes in fetuses with cardiac defects

Epigenetics in Cardiac Hypertrophy and Heart Failure

DNA methylation abnormalities of imprinted genes in congenital heart disease: A pilot study

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