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The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ATAC-Seq]

ABSTRACT: The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ATAC-Seq]

PROVIDER: PRJNA734788 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR14714553_1.fastq.gz	Fastqsanger.gz
	SRR14714553_2.fastq.gz	Fastqsanger.gz
	SRR14714554_1.fastq.gz	Fastqsanger.gz
	SRR14714554_2.fastq.gz	Fastqsanger.gz
	SRR14714555_1.fastq.gz	Fastqsanger.gz

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The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [RNA-Seq]

Project description:Mitochondrial metabolites regulate the function and differentiation of leukemic and normal stem cells by affecting epigenetic marks. However, it is less understood how mitochondrial enzymes localize to the nucleus to control stem cell function. We discovered that the mitochondrial metabolic enzyme Hexokinase 2 (HK2) localizes to the nucleus in leukemic and normal hematopoietic stem cells. Overexpression of nuclear HK2 increased leukemic stem cell (LSC) properties and decreased differentiation while selective knockdown of nuclear HK2 promoted differentiation and decreased stem cell function. The nuclear localization of HK2 was phosphorylation dependent and required active import and export. Nuclear HK2 regulated LSC and differentiation independent of its enzymatic and metabolic activity. HK2 interacted with nuclear proteins that regulate chromatin openness and increased chromatin accessibilities at sites associated with the LSC+ signature and DNA damage repair. Consistent with these effects, nuclear HK2 increased repair of DNA damage and contributed to the mechanism by which LSCs resist DNA damaging agents. Thus, we describe a non-canonical mechanism by which mitochondrial enzymes regulate gene expression and stem cell function independent of their metabolic function.

2022-03-15 | GSE176103 | GEO

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ChIP-Seq]

2022-03-15 | GSE176072 | GEO

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ATAC-Seq]

2022-03-15 | GSE176071 | GEO

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes

Project description:The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes

| PRJNA734918 | ENA

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [RNA-Seq]

Project description:The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [RNA-Seq]

| PRJNA735042 | ENA

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes [ChIP-Seq]

| PRJNA734789 | ENA

The mitochondrial metabolic enzyme Hexokinase 2 regulates stem cell function and differentiation by increasing chromatin openness and the accessibility of stem cell genes

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

2022-03-15 | GSE176104 | GEO

Hexokinase 2 and lactate

Project description:Hexokinase 2 and lactate

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Genome-wide maps of chromatin openness in control and LMNA R527C mutant MSCs

Project description:We performed ATAC-seq to examine to chromatin of openness of coding genes in healthy control and LMNA R527C patient-derived MSCs. The reduction of LADs did not increase the accessibility of the promoters flanking coding genes. The genome wide analysis of ATAC-seq showed that openness of coding genes related chromatin was decreased in mutant MSCs.Thus, R527C mutant Lamin A led to dysfunction of LADs and dysregulation of gene transcription, probably, leading to slow down or arrest of cell proliferation and differentiation.

2021-12-07 | GSE190195 | GEO

SALP, a new NGS library construction method especially useful for the high-throughput characterization of chromatin openness states

Project description:Background: Next-generation sequencing (NGS) is fundamental to the current biological and biomedical research. Construction of sequencing library is a key step of NGS. Therefore, various library construction methods have been explored. However, the current methods are still limited by some shortcomings. Results: This study developed a new NGS library construction method, Single strand Adaptor Library Preparation (SALP), by using a novel single strand adaptor (SSA). SSA is a double-stranded oligonucleotide with a 3ʹ overhang of 3 random nucleotides, which can be efficiently ligated to the 3′ end of single strand DNA by T4 DNA ligase. SALP can be started with any denatured DNA fragments such as those sheared by Tn5 tagmentation, enzyme digestion and sonication. When started with Tn5-tagmented chromatin, SALP can overcome a key limitation of ATAC-seq and become a high-throughput NGS library construction method, SALP-seq, which can be used to comparatively characterize the chromatin openness state of multiple cells unbiasly. In this way, this study successfully characterized the comparative chromatin openness states of four different cell lines, including GM12878, HepG2, HeLa and 293T, with SALP-seq. Similarly, this study also successfully characterized the chromatin openness states of HepG2 cells with SALP-seq by using 105 to 500 cells. Conclusions: This study developed a new NGS library construction method, SALP, by using a novel kind of single strand adaptor (SSA), which should has wide applications in the future due to its unique performance.

2018-01-31 | GSE104162 | GEO

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