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Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a

ABSTRACT: Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a

PROVIDER: PRJNA269642 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR2518150.fastq.gz	Fastqsanger.gz
	SRR2518170.fastq.gz	Fastqsanger.gz
	SRR2518180.fastq.gz	Fastqsanger.gz
	SRR2518190.fastq.gz	Fastqsanger.gz
	SRR2518200.fastq.gz	Fastqsanger.gz

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Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a [gene expression]

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. We used microarrays to detail the global program of gene expression after shControl, shPhf5a, or shPaf1 knockdown in mouse ESCs following 72h knockdown and identified distinct down-regulated and up-regulated genes during this process.

2016-08-31 | GSE73446 | GEO

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a.

Project description:Pluripotent embryonic stem cells (ESCs) self-renew or differentiate into all tissues of the developing embryo and cell-specification factors are necessary to balance gene expression. Here we delineate the function of the PHD-finger protein 5a (Phf5a) in ESC self-renewal and ascribe its role in regulating pluripotency, cellular reprogramming and myoblast specification. We demonstrate that Phf5a is essential for maintaining pluripotency, since depleted ESCs exhibit hallmarks of differentiation. Mechanistically, we attribute Phf5a function to the stabilization of the Paf1 transcriptional complex and control of RNA polymerase II elongation on pluripotency loci. Apart from an ESC-specific factor, we demonstrate that Phf5a controls differentiation of adult myoblasts. Our findings suggest a potent mode of regulation by Phf5a in stem cells, which directs their transcriptional programme, ultimately regulating maintenance of pluripotency and cellular reprogramming.

| S-EPMC5083132 | biostudies-literature

PHF5A coordinates p300 for epigenetic regulation of lipogenesis to promote hepatocellular carcinoma progression

Project description:PHD-finger protein 5A (PHF5A) is a component of U2snRNP, which plays a critical role in mRNA splicing for recognizing the branch site. However, whether it also plays other functions independent of RNA splicing remains elusive. Here, we find that expression levels of PHF5A are significantly upregulated in hepatocellular carcinoma (HCC). Down-regulation of PHF5A restrains liver cancer cell proliferation in vitro and in vivo. RNA-sequencing analysis reveals that fatty-acid biosynthetic enzymes are major downstream targets of PHF5A in HCC. Through metabolomics analysis, we find that inhibition of PHF5A reduces free fatty acid and phospholipid synthesis, further suppressing plasma membrane function. Mechanistically, PHF5A acts as a transcription co-factor of the p300 acetyltransferase for the H3K27 acetylation (Ac) and promotes H3K27Ac-dependent lipogenic genes expression. Our findings demonstrated a surprising splicing-independent role of PHF5A in transcriptional regulation of lipid metabolism for HCC progression and provided a new strategy for HCC therapy by blocking the interaction of PHF5A and p300.

2021-10-01 | GSE167023 | GEO

Characterization of histone modifications in mouse embryonic stem cells under control conditions or Phf5a knockdown

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. In this study we assayed for genome-wide localization of H3K4me3, H3K79me2 and H3K36me3 in mouse ESCs under conditions of shControl and shPhf5a knockdown. These results revealed that downregualtion of Phf5a results in the decrease of the elongation marks H3K79me2 and H3K36me3 from the gene bodies of pluripotency genes in ESC, wherease the promoter-associated mark H3K4me3 remains unaffected.

2016-08-31 | GSE73442 | GEO

Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a

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

2016-08-31 | GSE63974 | GEO

Acetylation of spliceosome protein PHF5A modulates stress responses and colorectal carcinogenesis through alternative splicing mediated upregulation of KDM3A

Project description:The process utilized by cancer cells for adapting to cellular stress is a key point for carcinogenesis. Alternative pre-mRNA splicing induced post-transcriptional gene expression regulation is one of the pathways for tumors maintaining proliferation rates accompanying the malignant phenotype under stress. However, the protein post-translational modification, especially protein acetylation on pre-mRNA splicing processes under stress is unknown. Here, we uncovered a list of hyperacetylated proteins in the context of acutely reduced Acetyl-CoA levels under nutrient starvation. PHD finger-like domain-containing protein 5A (PHF5A/SF3b14b), a component of U2 snRNPs, can be acetylated at lysine 29 in response to multiple cellular stresses. P300 and HDAC6 regulate PHF5A acetylation levels. PHF5A acetylation strengthens the interaction among U2 snRNPs, and affects global pre-mRNA splicing pattern and extensive gene expression. PHF5A hyperacetylation induced alternative splicing stabilizes KDM3A mRNA and promotes its protein expression. Pathologically, PHF5A K29 hyperacetylation and KDM3A upregulation axis are correlated with poor prognosis of colon cancer patients. Our findings uncovered a novel mechanism of anti-stress pathway that acetylation on PHF5A promotes the cancer cells capacity for stress resistance and consequently contributes to colon carcinogenesis.

2018-11-22 | GSE122761 | GEO

Opposing functions of H2BK120 ubiquitylation and H3K79 methylation in the regulation of pluripotency

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. In this study we assayed for genome-wide localization of H2BK120-ub in mouse ESCs under conditions of shControl and shPhf5a knockdown. These results revealed that downregualtion of Phf5a results in the increase of the elongation mark H2BK120-ub from the gene bodies of pluripotency genes in ESC.

2017-12-22 | GSE92727 | GEO

Nascent transript profiling upon in mouse embryonic stem cells under control conditions or Phf5a knockdown

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. In this study we assayed nascent RNA profiling using global run-on sequncing in mouse ESCs under conditions of self-renewal, differentiation and Phf5a knockdown. These results revealed that genes positively regulated by Paf1 in ESCs exibit RNA elongation pausing on their promoters. We used conditions of self-renewal, differentiation, Phf5a knockdown and Paf1 knockdown to monitor nascent transcript expression changes during Phf5a depletion using global run-on RNA sequencing (GRO-seq). These results revealed that Phf5a through the control of Paf1 complex regulates pause release and elongation of pluripoency-associated genes in embryonic stem cells.

2016-08-31 | GSE73441 | GEO

Mus musculus

Project description:Regulation of transcriptional elongation in pluripotency and cell differentiation by the PHD-finger protein Phf5a [gene expression]

| PRJNA297032 | ENA

Characterization of RNA Polymerase II occupancy in mouse embryonic stem cells under control conditions or Phf5a knockdown

Project description:Phf5a regulates transcription elongation in mouse embryonic stem cells (ESCs), through regulation of the Paf1 complex. In this study we assayed for genome-wide localization of Ser-5-phosphorylated RNA polymerase II and Ser-2-phosphorylated RNA polymerase II in mouse ESCs under conditions of shControl and shPhf5a knockdown. These results revealed that downregualtion of Phf5a results in the increase of the initiating form of RNA polymerase II (Ser5-phosphorylated) and in the aberrant loss of the elongating form of RNA polymerase II (Ser2-phosphorylated) of pluripotency genes in ESCs.

2016-08-31 | GSE73444 | GEO

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