Interplay of chromatin modifications and non-coding RNAs in the heart

Mathiyalagan, Prabhu; Keating, Samuel T.; Du, Xiao‐Jun; El‐Osta, Assam

doi:10.4161/epi.26405

Cited by 32 publications

(22 citation statements)

References 134 publications

(137 reference statements)

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“…Epigenetics modification plays a key role in the regulation of embryonic development and cardiogenesis [8–12]. Acetylation of histone generated by histone acetyltransferases (HATs) can neutralize the positive charges between histone and DNA allowing the binding of transcription factors to DNA, and consequently advances gene transcription [13, 14].…”

Section: Introductionmentioning

confidence: 99%

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Yan

Pan

et al. 2017

J Biomed Sci

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BackgroundPrenatal alcohol exposure may cause cardiac development defects, however, the underlying mechanisms are not yet clear. In the present study we have investigated the roles of histone modification by curcumin on alcohol induced fetal cardiac abnormalities during the development.Methods and resultsQ-PCR and Western blot results showed that alcohol exposure increased gene and active forms of caspase-3 and caspase-8, while decreased gene and protein of bcl-2. ChIP assay results showed that, alcohol exposure increased the acetylation of histone H3K9 near the promoter region of caspase-3 and caspase-8, and decreased the acetylation of histone H3K9 near the promoter region of bcl-2. TUNEL assay data revealed that alcohol exposure increased the apoptosis levels in the embryonic hearts. In vitro experiments demonstrated that curcumin treatment could reverse the up-regulation of active forms of caspase-3 and caspase-8, and down-regulation of bcl-2 induced by alcohol treatment. In addition, curcumin also corrected the high level of histone H3K9 acetylation induced by alcohol. Moreover, the high apoptosis level induced by alcohol was reversed after curcumin treatment in cardiac cells.ConclusionsThese findings indicate that histone modification may play an important role in mediating alcohol induced fetal cardiac apoptosis, possibly through the up-regulation of H3K9 acetylation near the promoter regions of apoptotic genes. Curcumin treatment may correct alcohol-mediated fetal cardiac apoptosis, suggesting that curcumin may play a protective role against alcohol abuse caused cardiac damage during pregnancy.

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Section: Introductionmentioning

confidence: 99%

Inhibition of histone acetylation by curcumin reduces alcohol-induced fetal cardiac apoptosis

Yan

Pan

et al. 2017

J Biomed Sci

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“…If proven to be causal pathways, HDAC inhibitors have the potential to become the first generation of epigenetic targeting agents in HF. Besides histone and DNA modifications, other mechanisms including RNA-based epigenetic regulations have been discovered [118,119]. How does different epigenetic mechanisms function together is also largely unknown.…”

Section: Expert Commentary and Five-year Viewmentioning

confidence: 99%

Epigenetic regulation and heart failure

Cao

2014

Expert Review of Cardiovascular Therapy

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Heart failure has become a huge public health problem. The treatment options for heart failure, however, are considerably limited. The significant disparity between the scope of a prominent health problem and the restricted means of therapy propagates heart failure epidemics. Delineating novel mechanisms of heart failure is imperative. Emerging evidence suggests that epigenetic regulation may take part in the pathogenesis of heart failure. Epigenetic regulation involves DNA and histone modifications that lead to changes in DNA-based transcriptional programs without altering the DNA sequence. Although more and more mechanisms are being discovered, the best understood epigenetic modifications are achieved through covalent biochemical reactions including histone acetylation, histone methylation and DNA methylation. Connecting environmental stimuli with genomic programs, epigenetic regulation remains important in maintaining homeostases and the pathogeneses of diseases. This review summarizes the most recent developments regarding individual epigenetic modifications and their implications in the pathogenesis of heart failure. Understanding this strategically important mechanism is potentially the key for developing powerful interventions in the future.

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“…89 Of interest, non-coding RNAs strictly cooperate with both acetyl-or methyl writing and erasing enzymes to edit chromatin conformation and gene expression. 90 It has been shown that microRNAs regulate the expression of both chromatin modifying enzymes as well as DNA methyl transferases (i.e.…”

Section: The Role Of Epigenetics In Cardiometabolic Diseasesmentioning

confidence: 99%