Browse
Submit Data
Databases
API
Help

Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

PHF3 regulates RNA stability through PHD and TLD domains - RNAseq PHD - TLD

ABSTRACT: Transcription and RNA processing are tightly coupled and precisely coordinated to ensure appropriate levels of mature transcripts. The C-terminal domain (CTD) of RNA polymerase II (Pol II) is phosphorylated differentially during the transcription cycle and serves as a landing pad for a variety of transcriptional regulators and RNA processing proteins. PHD finger protein 3 (PHF3) binds to the serine-2 phosphorylated Pol II CTD with its Spen Paralogue and Orthologue C-terminal (SPOC) domain and regulates transcription elongation and mRNA stability. Here we show that PHF3 binds target RNAs by recognizing a G-rich motif prone to form G-quadruplexes (G4s). Two PHF3 zinc finger domains, PHD (plant homeo domain) and TLD (TFIIS-like domain) act in concert to bind and destabilize target RNAs and their deletion in HEK293T cells causes massive deregulation of gene expression. Together these results establish PHF3 as a Pol II and an RNA-binding protein that coordinates transcription elongation with RNA decay to regulate neuronal gene expression.

INSTRUMENT(S): NextSeq 550

ORGANISM(S): Homo sapiens

SUBMITTER: Vedran Franke

PROVIDER: E-MTAB-14530 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

ACCESS DATA

Json Xml

Similar Datasets

PHF3 regulates RNA stability through PHD and TLD domains - m6A

2025-12-03 | E-MTAB-14529 | biostudies-arrayexpress

PHF3 regulates RNA stability through PHD and TLD domains - ChIPseq CNOT

2025-06-13 | E-MTAB-13125 | biostudies-arrayexpress

PHF3 binds G-rich RNAs and regulates RNA stability through its TFIIS-like domain (TLD) and plant homeodomain (PHD)

Project description:Transcription and RNA processing are tightly coupled and precisely coordinated to ensure appropriate levels of mature transcripts. The C-terminal domain (CTD) of RNA polymerase II (Pol II) is phosphorylated differentially during the transcription cycle and serves as a landing pad for a variety of transcriptional regulators and RNA processing proteins. PHD finger protein 3 (PHF3) binds to the serine-2 phosphorylated Pol II CTD with its Spen Paralogue and Orthologue C-terminal (SPOC) domain and regulates transcription elongation and mRNA stability. Here we show that PHF3 is an RNA-binding protein that recognizes a G-rich motif prone to form G-quadruplexes (G4s) within RNAs required for neurogenesis. We identify PHF3 TFIIS-like domain (TLD) as an RNA-binding domain, which shows nanomolar affinity for G-rich RNAs. TLD recruits PHF3 onto target RNAs and acts in concert with the plant homeodomain (PHD) to promote target RNA destabilization. PHF3 SPOC and PHD-TLD domains mediate interactions with various RNA-binding proteins (RBPs) that regulate mRNA stability. While PHF3 SPOC-dependent interactions with the m6A writer complex, splicing and elongation factors do not impact m6A RNA modification, alternative splicing or polyadenylation, PHF3 PHD-TLD domains interact with the PAF1 complex as a positive regulator of mRNA stability and interfere with its binding to Pol II. Our results establish PHF3 as an RNA-binding protein that binds G-rich RNAs through its TLD domain and destabilizes RNAs through PHD-TLD domains.

2025-09-26 | GSE278179 | GEO

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation - 3' RNA-seq

Project description:Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator (DIDO) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors, and tethers Pol II in a phase-separated microenvironment. Their SPOC domains and C-terminal intrinsically disordered regions are critical for transcription regulation. The dataset contains 3' Sequencing of WT, PHF3 KO, and PHF3 dSPOC mutant HEK293 cell line. Cytoplasmic and nuclear fractions were profiled separately.

2023-10-31 | E-MTAB-12757 | biostudies-arrayexpress

The SPOC proteins DIDO3 and PHF3 co-regulate gene expression and neuronal differentiation - RNAseq

Project description:Transcription is regulated by a multitude of activators and repressors, which bind to the RNA polymerase II (Pol II) machinery and modulate its progression. Death-inducer obliterator (DIDO) and PHD finger protein 3 (PHF3) are paralogue proteins that regulate transcription elongation by docking onto phosphorylated serine-2 in the C-terminal domain (CTD) of Pol II through their SPOC domains. Here we show that DIDO3 and PHF3 form a complex that bridges the Pol II elongation machinery with chromatin and RNA processing factors, and tethers Pol II in a phase-separated microenvironment. Their SPOC domains and C-terminal intrinsically disordered regions are critical for transcription regulation. PHF3 and DIDO exert cooperative and antagonistic effects on the expression of neuronal genes and are both essential for neuronal differentiation. The dataset contains RNAseq of HEK293 cells with various perturbations of PHF3 and DIDO1 genes.

2023-11-16 | E-MTAB-12782 | biostudies-arrayexpress

The SPOC domain is a phosphoserine binding module that bridges transcription machinery with co- and post-transcriptional regulators - ChIP-seq

Project description:The heptarepeats of the C-terminal domain of Pol II are extensively modified throughout the transcription cycle. The CTD coordinates RNA synthesis and processing by recruiting transcription regulation factors as well as RNA capping, splicing and 3’end processing factors. The SPOC domain of PHF3 was recently identified as a new CTD reader domain specifically binding to phosphorylated Serine-2 residues in adjacent CTD repeats. Here, we establish the SPOC domains of the human proteins DIDO, SHARP and RBM15 as phosphoserine binding modules that can act as CTD readers but also recognize other phosphorylated binding partners. We report the crystal structure of SHARP (SPEN) SPOC-CTD and identify the molecular determinants for its specific binding to phosphorylated Serine-5. PHF3 and DIDO SPOC domains preferentially interact with the Pol II elongation complex, while RBM15 and SHARP SPOC domains engage with the m6A writer and reader proteins. Our findings establish the SPOC domain as a major interface between the transcription machinery and regulators of transcription and co-transcriptional processes. Here we include ChIP seq data from SHARP and PHF3 with and without the SPOC domain.

2023-02-22 | E-MTAB-11506 | biostudies-arrayexpress

CTD tyrosine phosphorylation impairs termination factor recruitment to transcribing RNA polymerase II

Project description:ChIP-chip was performed to identify the genomic binding locations for the termination factors Nrd1, and Rtt103, and for RNA polymerase (Pol) II phosphorylated at the tyrosine 1 and threonine 4 position of its C-terminal domain (CTD). In different phases of the transcription cycle, Pol II recruits different factors via its CTD, which consists of heptapeptide repeats with the sequence Tyr1-Ser2-Pro3-Thr4-Ser5-Pro6-Ser7. Here we show that the CTD of transcribing yeast Pol II is phosphorylated at Tyr1, and that this impairs recruitment of termination factors. Tyr1 phosphorylation levels rise downstream of the transcription start site (TSS), and decrease before the polyadenylation (pA) site. Tyr1-phosphorylated gene bodies are depleted of CTD-binding termination factors Nrd1, Pcf11, and Rtt103. Tyr1 phosphorylation blocks CTD binding by these termination factors, but stimulates binding of elongation factor Spt6. These results show that CTD modifications can not only stimulate but also block factor recruitment, and lead to an extended CTD code for transcription cycle coordination.

2012-06-29 | E-MTAB-1060 | biostudies-arrayexpress

Pol II Ser7phospho ChIP-seq in mES cells

Project description:RNA Polymerase II transcribes protein-coding and many non-coding RNA genes in eukaryotes. The largest subunit of RNA Polymerase II, Rpb1, contains a hepta-peptide repeat on its C-terminal tail with three potential phosphorylation sites (Serine 2, Serine 5 and Serine 7). Mammalian Rpb1 contains 52 repeats. The phosphorylation events are catalyzed by specific protein kinases where the phosphorylation of specific residues is coupled to the transcription cycle. For example, the Cdk7 subunit of TFIIH phosphorylates both Serine 5 and Serine 7 during intiation and the Cdk9 subunit of P-TEFb phosphorylates Serine 2 during the transition into productive elongation. The dataset presented here is the genome-wide distribution of RNA Pol II with Serine 7 of the CTD phosphorylated in murine embryonic stem cells. This data, in addition to phospho-specific datasets generated in the same cell type in Rahl et al. Cell 2010 and Seila et al. Science 2008, represents the genome-wide distribution of multiple RNA Pol II isoforms in murine embryonic stem cells: total Pol II, hypophosphorylated CTD Pol II, Serine 2 phosphorylated CTD Pol II, Serine 5 phosphorylated CTD Pol II and Serine 7 phosphorylated CTD Pol II. An antibody specific to RNA Pol II Serine 7 phosphorylated CTD (gift of Dirk Eick; Chapman et al. Science 2008) was used to enrich for DNA fragments associated with this Pol II isoform in murine embryonic stem cells. DNA was purified and prepared for Illumina/Solexa sequencing following their standard protocol. This is a single dataset but together with datasets from Rahl et al. Cell 2010 and Seila et al. Science 2008, these datasets represent the genome-wide distribution of multiple RNA Pol II isoforms in murine embryonic stem cells: total Pol II, hypophosphorylated CTD Pol II, Serine 2 phosphorylated CTD Pol II, Serine 5 phosphorylated CTD Pol II and Serine 7 phosphorylated CTD Pol II.

2010-05-20 | E-GEOD-21917 | biostudies-arrayexpress

The conserved protein Seb1 from fission yeast is recruited to the chromatin during active Pol II transcription

Project description:The protein Seb1 from fission yeast contains a conserved CTD-interacting domain (CID) with which it can bind to phosphorylated forms of the Pol II C-terminal domain (CTD) during active transcription. It mainly interacts with Ser2P-CTD but also with Ser5P-CTD. Here, we show the recruitment profile of the protein to chromatin using ChIP-Seq which is mediated mainly via binding to the Pol II-CTD. In addition, it can also interact with nascent RNA via its RNA recognition motif (RRM) domain.

2017-02-14 | GSE93342 | GEO

RNA Polymerase II-associated factor 1 regulates the release and phosphorylation of paused RNA Polymerase II

Project description:Release of promoter-proximal paused RNA polymerase II (Pol II) during early elongation is a critical step in transcriptional regulation in metazoan cells. Paused Pol II release is thought to require the kinase activity of cyclin-dependent kinase 9 (CDK9) for the phosphorylation of DRB sensitivity-inducing factor, negative elongation factor, and C-terminal domain (CTD) serine-2 of Pol II. We found that Pol II-associated factor 1 (PAF1) is a critical regulator of paused Pol II release, that positive transcription elongation factor b (P-TEFb) directly regulates the initial recruitment of PAF1 complex (PAF1C) to genes, and that the subsequent recruitment of CDK12 is dependent on PAF1C. These findings reveal cooperativity among P-TEFb, PAF1C, and CDK12 in pausing release and Pol II CTD phosphorylation. Comparison of the chromatin occupancy of [1] PAF1, CDC73, LEO1, CTR9, total Pol II, and CTD serine 2-phosphorylated Pol II by ChIP-seq in THP1 cells; [2] PAF1, Pol II, Pol II (ser-5p), CDK12, and CDK9 by ChIP-seq in control and PAF1 knockdown cells; [3] LEO1 and Pol II by ChIP-seq in control and flavopiridol treated THP1 cells.

2015-12-11 | E-GEOD-62171 | biostudies-arrayexpress

OmicsDI is part of the ELIXIR infrastructure

OmicsDI is an Elixir interoperability service. Learn more ›

Tweets

OmicsDI Databases

PRIDE
PeptideAtlas
MassIVE
JPOST Repository
Physiome Model Repository

EGA
EVA
ENA
LINCS
PAXDB
Cell Collective

MetaboLights
Metabolomics Workbench
MetabolomeExpress
GNPS
BioModels
FAIRDOMHub

ArrayExpress
dbGaP
ExpressionAtlas
GEO
NODE

Information

Databases
Help
API
Contact us
Code on GitHub
Terms of use
Submit Data