The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

Yu, Shanshan; Li, Yihong; Zhao, Hongwei; Chen, Ping

doi:10.3389/fphys.2020.00539

Cited by 22 publications

(20 citation statements)

References 39 publications

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“… 35 Another lysine demethylase, KDM3C, has been also associated to cardiomyocyte hypertrophy response, where its knockdown inversely impacted angiotensin II-induced fetal gene program and cell growth. 37 KDM5C might also impacted hypertrophy-related gene program, however it should be further investigated by loss of function experiments.…”

Section: Discussionmentioning

confidence: 98%

Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells

Ahmadvand

Osia²,

Meyfour

et al. 2021

J Cardiovasc Thorac Res

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Introduction: Gender-specific phenotypes of the heart were reported with respect to both physiology and pathology. While most differences were associated with the sex hormones, differential expression of genes received special attention, particularly X-Y chromosomes’ genes. Methods: Here, we compared cardiogenesis by gene expression analysis of lineage specific markers and X-Y chromosomes’ genes, during in vitro differentiation of XY and XX human embryonic stem cells (hESC), in a hormone-free setup. Results: Downregulation of pluripotency marker (NANOG) and upregulation of cardiac mesoderm and progenitor markers (GATA4, TBX5, NKX2.5, ISL1) was remained temporally similar in differentiating XY and XX hESCs. Isoproterenol treatment of XY and XX hESC-derived cardiomyocytes (hESCCM) induced hypertrophy in a sex-specific manner, with female cardiomyocytes showing response at higher isoproterenol concentration and a later time point of differentiation. Interestingly, KDM5C as an X-linked gene, was markedly upregulated in both hypertrophied male and female cardiomyocytes. Conclusion: Collectively, our results indicated a temporally identical cardiogenesis, but more susceptibility of XY hESC-CM to hypertrophic stimulus in a hormone-free condition.

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Section: Discussionmentioning

confidence: 98%

Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells

Ahmadvand

Osia²,

Meyfour

et al. 2021

J Cardiovasc Thorac Res

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“…JMJD2A was overexpressed in hypertrophic heart tissues and promoted the development of cardiac hypertrophy via regulating H3K9me3 [ 9 ]. The histone demethylase JMJD1C regulated H3K27me to repress CAMKK2-AMPK signaling and promote cardiac hypertrophy [ 10 ]. Besides, NSD2 promoted ventricular remodeling mediated by the regulation of H3K36me2 [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…For instance, Jumonji domain-containing 2A (JMJD2A) promoted the development of pathological cardiac hypertrophy via regulating H3K9me3 and expression of four-and-a-half LIM domains 1 [ 9 ]. The histone demethylase JMJD1C was also reported to modulate CAMKK2-AMPK signaling to contribute to cardiac hypertrophy [ 10 ]. H3K9me2-specific demethylase KDM3A promoted cardiac hypertrophy and fibrosis in response to pressure-overload.…”

Section: Introductionmentioning

confidence: 99%

PHD Finger Protein 19 Promotes Cardiac Hypertrophy via Epigenetically Regulating SIRT2

Cheng

Wang

et al. 2021

Cardiovasc Toxicol

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Epigenetic regulations essentially participate in the development of cardiomyocyte hypertrophy. PHD finger protein 19 (PHF19) is a polycomb protein that controls H3K36me3 and H3K27me3. However, the roles of PHF19 in cardiac hypertrophy remain unknown. Here in this work, we observed that PHF19 promoted cardiac hypertrophy via epigenetically targeting SIRT2. In angiotensin II (Ang II)-induced cardiomyocyte hypertrophy, adenovirus-mediated knockdown of Phf19 reduced the increase in cardiomyocyte size, repressed the expression of hypertrophic marker genes Anp and Bnp, as well as inhibited protein synthesis. By contrast, Phf19 overexpression promoted Ang II-induced cardiomyocyte hypertrophy in vitro. We also knocked down Phf19 expression in mouse hearts in vivo. The results demonstrated that Phf19 knockdown reduced Ang II-induced decline in cardiac fraction shortening and ejection fraction. Phf19 knockdown also inhibited Ang II-mediated increase in heart weight, reduced cardiomyocyte size, and repressed the expression of hypertrophic marker genes in mouse hearts. Further mechanism studies showed that PHF19 suppressed the expression of SIRT2, which contributed to the function of PHF19 during cardiomyocyte hypertrophy. PHF19 bound the promoter of SIRT2 and regulated the balance between H3K27me3 and H3K36me3 to repress the expression of SIRT2 in vitro and in vivo. In human hypertrophic hearts, the overexpression of PHF19 and downregulation of SIRT2 were observed. Of importance, PHF19 expression was positively correlated with hypertrophic marker genes ANP and BNP but negatively correlated with SIRT2 in human hypertrophic hearts. Therefore, our findings demonstrated that PHF19 promoted the development of cardiac hypertrophy via epigenetically regulating SIRT2.

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“…Given the extensive changes in functional gene expression observed in CnATg hearts, and the known observation that H3K4 and H3K9 trimethyl marks are decreased genome wide in heart disease patients [16] we wondered if epigenetic regulation was aberrant in CnTg hearts. We and others have previously established the contribution of members of the Jumonji histone demethylase family in models of mechanical overload by transaortic constriction (TAC) [14,15] [6] [11,34]. We therefore examined mRNA and protein levels of multiple Jumonji demethylases including those that remove H3K4 or H3K9 methylation.…”

Section: Epigenetic Erasers Controlling Histone Methylation Are Upregulated In Cnatg Heartsmentioning

confidence: 99%

Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival

Tran

Zhang

Wang

et al. 2022

Journal of Biological Chemistry

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show abstract

The Histone Demethylase JMJD1C Regulates CAMKK2-AMPK Signaling to Participate in Cardiac Hypertrophy

Cited by 22 publications

References 39 publications

Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells

Gender-specific characteristics of hypertrophic response in cardiomyocytes derived from human embryonic stem cells

PHD Finger Protein 19 Promotes Cardiac Hypertrophy via Epigenetically Regulating SIRT2

Inhibition of Jumonji demethylases reprograms severe dilated cardiomyopathy and prolongs survival

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