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Mus musculus

ABSTRACT: CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [HiC-Seq]

PROVIDER: PRJNA353555 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5016460_1.fastq.gz	Fastqsanger.gz
	SRR5016460_2.fastq.gz	Fastqsanger.gz
	SRR5016461_1.fastq.gz	Fastqsanger.gz
	SRR5016461_2.fastq.gz	Fastqsanger.gz
	SRR5016462_1.fastq.gz	Fastqsanger.gz

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CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [HiC-Seq]

Project description:We found that aspects of the IL-2-sensitive effector gene program in CD4+ Th1 and CD8+ Tc1 cells are regulated by glutamine and alpha-ketoglutarate (αKG)-induced events, in part through changes in DNA and histone methylation states. We further identified a novel mechanism by which IL-2- and αKG-sensitive metabolic changes regulate the association of CTCF with select genomic sites. αKG-sensitive CTCF sites were often associated with loci containing IL-2- and αKG-sensitive genome organization patterns and gene expression in T cells. Surprisingly, IL-2- and αKG-sensitive CTCF sites in T cells were also associated with genes from developmental pathways that had αKG-sensitive expression in ES cells. The data collectively support a novel mechanism wherein CTCF serves to translate αKG-sensitive metabolic changes into context-dependent differentiation gene programs.

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CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ATAC-Seq]

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CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ChIP-Seq]

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Project description:CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ChIP-Seq]

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Project description:CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [RNA-Seq]

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Project description:CTCF translates IL-2- and αKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs [ATAC-Seq]

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CTCF translates IL-2- and aKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs

Project description:CTCF translates IL-2- and aKG-sensitive metabolic changes in T cells into context-dependent differentiation gene programs

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Mitochondrial Calcium Exchange links Metabolism with the Epigenome to Control Cellular Differentiation (ATAC-seq)

Project description:Fibroblast to myofibroblast differentiation is crucial for the initial healing response but excessive myofibroblast activation leads to pathological fibrosis. Therefore, it is imperative to understand the mechanisms underlying myofibroblast formation. Here we report that mitochondrial calcium (mCa2+) signaling is a regulatory mechanism in myofibroblast differentiation and fibrosis. We demonstrate that inhibition of mCa2+ uptake in fibroblasts enhances myofibroblast formation and this translates to increased fibrosis following injury. Fibrotic signaling alters the gating of the mitochondrial calcium uniporter (mtCU) to reduce mCa2+ uptake and induce specific changes in metabolism. mCa2+-dependent metabolic reprogramming leads to the activation of αKG-dependent demethylases which epigenetically modify promoter regions specific to the myofibroblast gene program resulting in differentiation. Our results uncover an important role for mCa2+ uptake beyond metabolic regulation and cell death and demonstrate that mCa2+ signaling regulates the epigenome to influence cellular differentiation.

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