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The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [RNA-seq]

ABSTRACT: The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [RNA-seq]

PROVIDER: PRJNA1043591 | ENA |

REPOSITORIES: ENA

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			Action	DRS
	SRR26899000_1.fastq.gz	Fastqsanger.gz
	SRR26899000_2.fastq.gz	Fastqsanger.gz
	SRR26899001_1.fastq.gz	Fastqsanger.gz
	SRR26899001_2.fastq.gz	Fastqsanger.gz
	SRR26899002_1.fastq.gz	Fastqsanger.gz

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The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [ChIP-seq]

Project description:The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [ChIP-seq]

| PRJNA1043592 | ENA

The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [RNA-seq]

Project description:RNA polymerase II (RNAPII) transcription elongation directs an intricate pattern of histone modifications. Formation of this pattern involves a highly conserved regulatory axis, key components of which are the elongation factor Rtf1, monoubiquitylation of histone H2B (H2Bub1), and methylation of histone H3 on lysine 4 (H3K4me). Direct contact between Rtf1 and the ubiquitylation complex Rad6-Bre1 stimulates H2Bub1, which in turn promotes H3K4me by stimulating the activity of the Set1C/COMPASS methyltransferase complex. Previous studies have defined the molecular basis for these regulatory relationships, but it remains unclear how they regulate chromatin and transcription in vivo. We found that mutations affecting multiple components of the Rtf1-H2Bub1-H3K4me axis in the model eukaryote Schizosaccharomyces pombe caused resistance to the ribonucleotide reductase inhibitor hydroxyurea (HU). Resistance correlated with a reduced effect of HU on dNTP pools, bypass of the S-phase checkpoint in the presence of HU, and blunting of the transcriptional response to HU treatment. Mutations in the C-terminal repeat domain (CTD) of the RNAPII large subunit Rpb1 led to a similar spectrum of phenotypes. Moreover, all the HU resistant mutants we identified also exhibited resistance to several azole class antifungal agents. Our results suggest a novel, shared gene regulatory function of the Rtf1-H2Bub1-H3K4me axis and the Rpb1 CTD in controlling fungal drug tolerance.

2023-11-27 | GSE248361 | GEO

The Rtf1/Prf1-dependent histone modification axis and Rpb1 C-terminal domain phosphorylation counteract multi-drug resistance in fission yeast [ChIP-seq]

2023-11-27 | GSE248360 | GEO

Expression profiling of rpb1-12XWTCTD and rpb1-12XS2ACTD fission yeast strains.

Project description:In fission yeast, the nuclear-localized Lsk1p-Lsc1p-Lsg1p cyclin dependent kinase complex is required for the reliable execution of cytokinesis and is also required for Ser-2 phosphorylation RNA pol II carboxy terminal domain. To address whether alterations in CTD phosphorylation might selectively alter expression of cytokinesis genes, expression profiling of site-directed CTD mutants was performed. Strains bearing the rpb1-12XCTD and rpb1-12XS2ACTD mutations were grown to mid-log phase in YES media and treated with 0.5uM LatA (or the solvent control, DMSO) for three hours at 30C. Three biological replicates were performed.

2011-08-31 | E-GEOD-31369 | biostudies-arrayexpress

Expression profiling of rpb1-12XWTCTD and rpb1-12XS2ACTD fission yeast strains.

2011-09-01 | GSE31369 | GEO

Rtf1-dependent transcriptional pausing regulates cardiogenesis

Project description:During heart development, an evolutionarily conserved network of cardiac transcription factors collaborate to define the precise timing and location of cardiac progenitor specification. Accumulating evidence suggests that cardiac progenitor specification is subject to transcriptional control beyond the level of transcription initiation. The PAF1C component Rtf1 is a multifunctional transcription regulatory protein that modulates pausing and elongation of RNA Pol II, as well as histone epigenetic modifications. By transient knockdown and CRISPR mutagenesis, we found that Rtf1 is essential for cardiogenesis and that without Rtf1 activity, cardiac progenitors arrest in an immature state. This role in early cardiogenesis was evolutionarily conserved between fish and mammals. We also found that Rtf1's Plus3 domain, which confers interaction with the pausing/elongation factor Spt5, was required for Rtf1's ability to support cardiac progenitor formation, while other regions of the protein were dispensable. We examined the occupancy of RNA Pol II at cardiac genes in rtf1 morphants using ChIP-seq and found that Pol II signals at the TSS of genes was reduced, suggesting a reduction in transcriptional pausing. Intriguingly, pharmacological or morpholino antisense reduction of pause release in rtf1 morphants and mutants restored the formation of cardiac cells and improved Pol II occupancy at the TSS of key cardiac genes. Our findings highlight the crucial role that transcriptional pausing plays in promoting normal levels of gene expression in a cardiac developmental context.

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Modification of C-terminal Domain (CTD) of RPB1 plays a role in transcriptome change upon salt stress

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Modification of C-terminal Domain (CTD) of RPB1 plays a role in transcriptome change upon salt stress

2014-12-03 | E-GEOD-60700 | biostudies-arrayexpress

N-terminal tagging of RNA Polymerase II shapes transcriptomes more than C-terminal alterations

Project description:To investigate the effect of RPB1 CTD length on transcription dynamics, six mutant U2OS cell lines expressing tagged versions of α-amanitin resistant RPB1 with CTDs of varying lengths (Dendra2-RPB1-25R (D25), Dendra2-RPB1-52R (D52), Dendra2-RPB1-70R (D70), HaloTag-RPB1-25R (H25), HaloTag-RPB1-52R (H52), and HaloTag-RPB1-70R (H70)) were grown in α-amanitin to degrade endogenous RPB1, then their RNA was sequenced at single-cell resolution using a droplet-based system.

2024-05-12 | GSE217243 | GEO

RTF1 mediates epigenetic control of Th17 cell differentiation via H2B monoubiquitination [RNA-seq]

Project description:The transcription factor RTF1 has been identified as a gene associated with an increased risk of ulcerative colitis (UC) . In this study, we investigated its impact on modulating intestinal inflammation through the control of T cells expressing interleukin-17A (Th17) cells. Our results demonstrate that RTF1 deficiency disrupts the differentiation of Th17 cells, while leaving regulatory T cells (Treg) cells unaffected. Mechanistically, RTF1 facilitates Histone H2B monoubiquitination (H2Bub1), which requires its histone modification domain (HMD). Impaired Th17 differentiation was also observed in cells lacking the H2Bub1 E3 ligase subunit RNF40. This study underscores the essential role of RTF1 in H2Bub1-mediated epigenetic regulation of Th17 cell differentiation. Understanding this process provides valuable insight into addressing Th17-associated inflammatory disorders.

2025-04-03 | GSE269436 | GEO

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