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PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage

ABSTRACT: PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage

PROVIDER: PRJNA395422 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR5860260.fastq.gz	Fastqsanger.gz
	SRR5860270.fastq.gz	Fastqsanger.gz
	SRR5860261.fastq.gz	Fastqsanger.gz
	SRR5860271.fastq.gz	Fastqsanger.gz
	SRR5860262.fastq.gz	Fastqsanger.gz

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Similar Datasets

PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [Repli-Seq]

Project description:Down-regulation (DR) of PREP1 (aka PKNOX1) tumor suppressor induces H2Ax foci in human fibroblasts. Here we have analyzed the effect of PREP1 DR on DNA replication using cell cycle analysis, Repliseq, DNA combing, ChIP-seq, RNA-seq and immunofluorescence (IF). In human cells, PREP1 DR similarly affects both the rate of DNA replication and the progression of cells through the S phase. Genome wide, PREP1 DR induces late to early DNA replication shifts in normally late-replicated genomic regions amounting to 25% of the genome, in addition to unscheduled origins firing. A concomitant strong increase of unidirectional replication forks explains the appearance of DNA damage foci. The DNA target of PREP1 DR is the Lamin Associated DNA, in agreement with the simultaneous decrease of Lamin B1. Therefore PREP1 is a novel regulator of replication timing and Lamin B1 level, which ChIP-seq and RNA-seq data indicate as independent from its transcriptional activity. This activity must constitute the basis for its tumor suppression function.

2018-02-28 | GSE101775 | GEO

PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [RNA-Seq]

2018-02-28 | GSE101774 | GEO

PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [ChIP-Seq]

2018-02-28 | GSE101773 | GEO

Prep1 prevents premature adipogenesis of mesenchymal progenitors [ChIP-seq]

Project description:Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 pre-adipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBPß(CAAT enhancer binding protein ß) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBPß.

2017-12-06 | GSE100055 | GEO

Prep1 prevents premature adipogenesis of mesenchymal progenitors [RNA-seq]

Project description:Transcriptional regulators are crucial in adipocyte differentiation. We now show that the homeodomain-containing transcription factor Prep1 is a repressor of adipogenic differentiation since its down-regulation (DR) in both ex vivo bone marrow-derived mesenchymal stromal cells (MSC) and in vitro 3T3-L1 pre-adipocytes significantly increases their adipogenic differentiation ability. Prep1 acts at a stage preceding the activation of the differentiation machinery because its DR makes cells more prone to adipogenic differentiation even in the absence of the adipogenic inducers. Prep1 DR expands the DNA binding landscape of C/EBP(CAAT enhancer binding protein ) without affecting its expression or activation. The data indicate that Prep1 normally acts by restricting DNA binding of transcription factors to adipogenic enhancers, in particular C/EBP.

2017-12-06 | GSE100056 | GEO

PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage

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

2018-02-28 | GSE101776 | GEO

Gene expression from Prep1-ablated mice

Project description:The homeodomain transcription factor Prep1 was previously shown to regulate insulin sensitivity. Our aim was to study the specific role of Prep1 for the regulation of energy metabolism in skeletal muscle. Muscle specific ablation of Prep1 resulted in increased expression of respiratory chain subunits. This finding was consistent with an increase in mitochondrial enzyme activity without affecting mitochondrial volume fraction as assessed by electron microscopy. Metabolic phenotyping revealed no differences in daily energy expenditure or body composition. However, during treadmill exercise challenge, Prep1 ablation resulted in a higher maximal oxidative capacity and better endurance. Elevated PGC-1α expression was identified as a cause for increased mitochondrial capacity in Prep1-ablated mice. Prep1 stabilizes p160 Mybbp1a, a known inhibitor of PGC-1α activity. Thereby, P160 protein levels were significantly lower in muscle of Prep1-ablated mice. By a ChIPseq approach, PREP1-binding sites in genes encoding mitochondrial components (e.g. Ndufs2) were identified that might be responsible for elevated OXPHOS proteins in the muscle of Prep1 nullmutants. These results suggest that Prep1 exhibits additional direct effects on regulation of mitochondrial proteins. We therefore conclude that Prep1 is a regulator of oxidative phosphorylation components via direct and indirect mechanisms.

2014-01-01 | GSE52424 | GEO

Homo sapiens

Project description:PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [RNA-Seq]

| PRJNA395426 | ENA

Homo sapiens

Project description:PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [ChIP-Seq]

| PRJNA395427 | ENA

Homo sapiens

Project description:PREP1 down-regulation changes the DNA replication timing of Lamin-associated DNA and induces DNA damage [Repli-Seq]

| PRJNA395425 | ENA