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KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [CUT&Tag]

ABSTRACT: KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [CUT&Tag]

PROVIDER: PRJNA890624 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR21904856_1.fastq.gz	Fastqsanger.gz
	SRR21904856_2.fastq.gz	Fastqsanger.gz
	SRR21904857_1.fastq.gz	Fastqsanger.gz
	SRR21904857_2.fastq.gz	Fastqsanger.gz
	SRR21904858_1.fastq.gz	Fastqsanger.gz

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KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [CUT&Tag]

Project description:Cardiac metabolism is deranged in heart failure, but underlying mechanisms remain unclear. Lysine demethylase 8 (Kdm8) represses gene expression in the embryo and controls metabolism in cancer. However, its function in cardiac homeostasis is unknown. We show that Kdm8 maintains a mitochondrial gene network active by repressing Tbx15 to prevent dilated cardiomyopathy leading to lethal heart failure. Deletion of Kdm8 in mouse cardiomyocytes increased H3K36me2 with activation of Tbx15 and repression of target genes in the NAD+ pathway before dilated cardiomyopathy initiates. Moreover, NAD+ supplementation prevented dilated cardiomyopathy in Kdm8 mutant mice and TBX15 overexpression blunted NAD+-activated cardiomyocyte respiration. Furthermore, KDM8 was downregulated in human hearts affected by dilated cardiomyopathy and higher TBX15 expression defines a subgroup of affected hearts with the strongest downregulation of genes encoding mitochondrial proteins. Thus, KDM8 represses TBX15 to maintain cardiac metabolism. Our results suggest that epigenetic dysregulation of metabolic gene networks initiates myocardium deterioration towards heart failure and could underlie heterogeneity of dilated cardiomyopathy.

2022-12-23 | GSE215793 | GEO

KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy

Project description:KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy

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KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [RNA-seq]

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KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [RNA-seq]

Project description:KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy [RNA-seq]

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Project description:This study attempts at investigating the changes in cardiac gene expression that occur in Dilated Cardiomyopathy (DCM). DCM in Dobermans and Boxers are the focus of this study. Control heart tissue as well as Pacing tissue used is from mongrel dogs. Keywords: control vs pacing vs disease; strain specific disease 3 Dobermans-DCM, 4 Boxers-DCM, 3 mongrels-control and 3 mongrels-pacing

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KDM8 epigenetically controls cardiac metabolism to prevent initiation of dilated cardiomyopathy

Project description:This SuperSeries is composed of the SubSeries listed below.

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