Histone lysine methylation and congenital heart disease: From bench to bedside (Review)

Yi, Xin; Jiang, Xuejun; Li, Xiaoyan; Jiang, Ding‐Sheng

doi:10.3892/ijmm.2017.3115

Cited by 24 publications

(16 citation statements)

References 171 publications

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“…SMYD proteins in mammals are located in both the cytoplasm and the nucleus, and correspondingly have the ability to methylate both histone and non-histone targets (Brown et al 2006;Gottlieb et al 2002;Hamamoto et al 2004;Huang et al 2006;Mazur et al 2014;Tracy et al 2018;Yi et al 2017). SMYD1 was also detected in both the cytoplasm and the macronucleus (and possibly micronucleus) in Tetrahymena cells, which is consistent with its localization in mammalian systems.…”

Section: Smyd Is Involved In the Regulation Of Metabolism-related Gensupporting

confidence: 72%

Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila

Zhao

Duan

et al. 2020

Mar Life Sci Technol

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Lysine methylation of histones and non-histones plays a pivotal role in diverse cellular processes. The SMYD (SET and MYND domain) family methyltransferases can methylate various histone and non-histone substrates in mammalian systems, implicated in HSP90 methylation, myofilament organization, cancer inhibition, and gene transcription regulation. To resolve controversies concerning SMYD's substrates and functions, we studied SMYD1 (TTHERM_00578660), the only homologue of SMYD in the unicellular eukaryote Tetrahymena thermophila. We epitope-tagged SMYD1, and analyzed its localization and interactome. We also characterized ΔSMYD1 cells, focusing on the replication and transcription phenotype. Our results show that: (1) SMYD1 is present in both cytoplasm and transcriptionally active macronucleus and shuttles between cytoplasm and macronucleus, suggesting its potential association with both histone and non-histone substrates; (2) SMYD1 is involved in DNA replication and regulates transcription of metabolism-related genes; (3) HSP90 is a potential substrate for SMYD1 and it may regulate target selection of HSP90, leading to pleiotropic effects in both the cytoplasm and the nucleus.

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Section: Smyd Is Involved In the Regulation Of Metabolism-related Gensupporting

confidence: 72%

Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila

Zhao

Duan

et al. 2020

Mar Life Sci Technol

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“…Previous research has shown that both HMTs and histone demethyltransferases may be implicated in CHD pathogenesis . However, evidence of HMT involvement in alcohol‐induced CHD development is lacking.…”

Section: Discussionmentioning

confidence: 99%

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

Peng

Han

Chang

et al. 2019

J Cellular Molecular Medi

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Alcohol consumption during pregnancy can cause foetal alcohol syndrome and congenital heart disease. Nonetheless, the underlying mechanism of alcohol‐induced cardiac dysplasia remains unknown. We previously reported that alcohol exposure during pregnancy can cause abnormal expression of cardiomyogenesis‐related genes, and histone H3K9me3 hypomethylation was observed in alcohol‐treated foetal mouse heart. Hence, an imbalance in histone methylation may be involved in alcohol‐induced cardiac dysplasia. In this study, we investigated the involvement of G9α histone methyltransferase in alcohol‐induced cardiac dysplasia in vivo and in vitro using heart tissues of foetal mice and primary cardiomyocytes of neonatal mice. Western blotting revealed that alcohol caused histone H3K9me3 hypomethylation by altering G9α histone methyltransferase expression in cardiomyocytes. Moreover, overexpression of cardiomyogenesis‐related genes (MEF2C, Cx43, ANP and β‐MHC) was observed in alcohol‐exposed foetal mouse heart. Additionally, we demonstrated that G9α histone methyltransferase directly interacted with histone H3K9me3 and altered its methylation. Notably, alcohol did not down‐regulate H3K9me3 methylation after G9α suppression by short hairpin RNA in primary mouse cardiomyocytes, preventing MEF2C, Cx43, ANP and β‐MHC overexpression. These findings suggest that G9α histone methyltransferase‐mediated imbalance in histone H3K9me3 methylation plays a critical role in alcohol‐induced abnormal expression cardiomyogenesis‐related genes during pregnancy. Therefore, G9α histone methyltransferase may be an intervention target for congenital heart disease.

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“…To date, researchers have conducted extensive investigations on cardiovascular disease at the genetic and epigenetic levels, and these studies have greatly deepened our understanding of cardiovascular disease [4][5][6][7][8][9][10][11]. Most conventional therapies available for patients with cardiovascular disease involve protein-targeting drugs.…”

Section: Introductionmentioning

confidence: 99%

RNA Modification by m6A Methylation in Cardiovascular Disease

Wei

Jiang

2021

Oxidative Medicine and Cellular Longevity

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Cardiovascular disease is currently the leading cause of death worldwide, and its underlying regulatory mechanisms remain largely unknown. N6-Methyladenosine (m6A) RNA methylation is an epigenetic modification involved in the splicing, nuclear export, translational regulation, and degradation of RNA. After the initial identification of m6A RNA methylation in 1974, the rise of next-generation sequencing technology to detect m6A throughout the transcriptome led to its renewed recognition in 2012. Since that time, m6A methylation has been extensively studied, and its functions, mechanisms, and effectors (e.g., METTL3, FTO, METTL14, WTAP, ALKBH5, and YTHDFs) in various diseases, including cardiovascular diseases, have rapidly been investigated. In this review, we first examine and summarize the molecular and cellular functions of m6A methylation and its readers, writers, and erasers in the cardiovascular system. Finally, we discuss future directions for m6A methylation research and the potential for therapeutic targeting of m6A modification in cardiovascular disease.

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Histone lysine methylation and congenital heart disease: From bench to bedside (Review)

Cited by 24 publications

References 171 publications

Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila

Functional analysis of the methyltransferase SMYD in the single-cell model organism Tetrahymena thermophila

G9α‐dependent histone H3K9me3 hypomethylation promotes overexpression of cardiomyogenesis‐related genes in foetal mice

RNA Modification by m6A Methylation in Cardiovascular Disease

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