Homo sapiens
Ontology highlight
ABSTRACT:
PROVIDER: PRJNA238510 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR1169714_1.fastq.gz | Fastqsanger.gz | |||
| SRR1169714_2.fastq.gz | Fastqsanger.gz | |||
| SRR1169715_1.fastq.gz | Fastqsanger.gz | |||
| SRR1169715_2.fastq.gz | Fastqsanger.gz | |||
| SRR1169716_1.fastq.gz | Fastqsanger.gz |
Items per page: 5 1 - 5 of 12 |
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Project description:Activation of the P-TEFb Complex by Lethal Prostate Cancer-Associated Enhancer RNAs
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Project description:Activation of P-TEFb by enhancer RNAs associated with lethal prostate cancer [ChIP-seq]
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Project description:Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. We identify aan HIV-1 TAR-like (TAR-L) motif in AR-eRNAs of AR target genes including KLK3 (or PSA) and TMPRSS2. The TAR-L motif is important for these eRNAs to bind to CYCLIN T1 of the positive transcription elongation factor b (P-TEFb) complex. Knockdown of PSA eRNA diminishes RNA polymerase II (Pol II) serine-2 (Ser-2) phosphorylation at the PSA promoter. The TAR-L motif in KLK3 eRNA is crucial for effective transcription of PSA mRNA. Together, wWe demonstrate a P-TEFb activation function of eRNA and reveal aberrant eRNA expression as a functional indicator of AR abnormality in CRPC. Our results also suggest that eRNAs as amay be a potential target for CRPC therapy. Androgen receptor (AR) binding sites in human prostate cancer cell lines, LNCaP and C4-2, were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2016-02-12 | E-GEOD-55031 | biostudies-arrayexpress
Project description:Castration resistant prostate cancer (CRPC) is a lethal disease. Sustained aberrant activation of androgen receptor (AR) becomes a central mechanism that contributes to endocrine therapy resistance. Here, we demonstrate that AR-bound enhancer RNAs (AR-eRNAs), including eRNA of the KLK3 (or PSA) gene, are upregulated in human CRPC cells and patient tissues. By enhancing C-termine domain (CTD) serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p), PSA eRNA acts in cis to promote PSA mRNA transcription and in trans to induce mRNA expression of a large set of genes involved in androgen action, cell cycle progression and tumorgenesis. Accordingly, we demonstrate that PSA eRNA binds in vitro and in vivo to CYCLIN T1, a regulatory subunit of the positive transcription elongation factor b (P-TEFb) complex that mediates Pol II-Ser2p. To identify the PSA eRNAâ??s functions on the Pol II-Ser2p and CYCLINT1 in the CRPC C4-2 cells, we detected the Pol II-Ser2p and CYCLINT1 ChIP-seq with or without PSA eRNA knockdown in the C4-2 cells. Moreover, to rule out the AR binding changes and identify the AR binding sites around the new genes, we detected the AR ChIP-seq in LNCaP and C4-2 cells with or without the androgen. Androgen receptor (AR) binding sites in human prostate cancer cell lines, LNCaP and C4-2, were studied using ChIP-seq. Pol II Ser-2p and CYCLINT1 binding sites in human prostate cancer cell lines C4-2 with or without PSA eRNA knockdown, were studied using ChIP-seq. ChIP enriched and input DNA were sequenced using Illumina HiSeq 2000.
2016-02-12 | E-GEOD-65066 | biostudies-arrayexpress
Project description:Castration resistant prostate cancer (CRPC) is a lethal disease1-4. Aberrant activation of the androgen receptor (AR) becomes a central mechanism contributing to the resistance of endocrine therapies2,3. Here we demonstrate that non-coding RNAs transcribed from the AR bound-enhancers RNAs (AR-eRNAs) are upregulated in human CRPC cells in vitro, xenografts in vivo and patient tissues. Expression of a subset of genes with elevated AR-eRNAs, including TLE1 and HTR3A, is inversely correlated with biochemical recurrence-free survival of CRPC patients. We identify aan HIV-1 TAR-like (TAR-L) motif in AR-eRNAs of AR target genes including KLK3 (or PSA) and TMPRSS2. The TAR-L motif is important for these eRNAs to bind to CYCLIN T1 of the positive transcription elongation factor b (P-TEFb) complex. Knockdown of PSA eRNA diminishes RNA polymerase II (Pol II) serine-2 (Ser-2) phosphorylation at the PSA promoter. The TAR-L motif in KLK3 eRNA is crucial for effective transcription of PSA mRNA. Together, wWe demonstrate a P-TEFb activation function of eRNA and reveal aberrant eRNA expression as a functional indicator of AR abnormality in CRPC. Our results also suggest that eRNAs as amay be a potential target for CRPC therapy. Total RNA sequencing of two prostate cancer cells. Data were generated by deep sequencing, in diplicate, using Illumina HiSeq 2000.
2016-02-12 | E-GEOD-55030 | biostudies-arrayexpress
Project description:The evidence that several signal and ligand-dependent pathways function by activating regulatory enhancer programs suggests that a “checkpoint” strategy may underline activation of some or even many diversely-regulated enhancers. Here, we report a molecular mechanism common to several acute signal- and ligand-dependent enhancer activation programs based on release of a shared eRNA transcription checkpoint. This requires recruitment of a DNA-PKcs-phosphorylated RING finger repressor, KAP1, functioning as a modulator, inhibiting its association with 7SK and E3 SUMO ligase activity on the CDK9 subunit of P-TEFb, facilitating formation of an activated P-TEFb complex, licensing eRNA elongation. Overcoming this checkpoint for signal-dependent enhancer activation occurs in diverse pathways including estrogen receptor α, NF-κB-regulated proinflammatory, androgen receptor and neuronal depolarization. Therefore, a specific strategy required to convert a basal state enhancer P-TEFb complex to an active state to release a conserved checkpoint is apparently employed by several functionally-important signal/ligand-regulated regulatory enhancers to implement the instructions of endocrine/paracrine system
2025-02-21 | PXD056186 | Pride
Project description:Androgen receptor (AR) is required for castration resistant prostate cancer (CRPC) progression, but the function and disease relevance of AR-bound enhancers remain poorly understood. Here, we identify a group of AR-regulated enhancer RNAs (e.g. PSA eRNA) that are upregulated in CRPC cells, patient-derived xenografts (PDX) and patient tissues. PSA eRNA binds to CYCLIN T1, activates P-TEFb and promotes in cis and trans gene transcription by increasing serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p). To avoid the total Pol II changing by PSA eRNA. We measured the total Pol II using N20 and 8WG16 antibodies with or without PSA eRNA knocking down. To avoid the AR binding changes by PSA eRNA, we also measured the AR binding using AR N20 antibodies with or without PSA eRNA knocking down. Androgen receptor (AR) binding sites in human prostate cancer cell lines, C4-2, were studied using ChIP-seq. Total Pol II Ser-2p and AR binding sites in human prostate cancer cell lines C4-2 with or without PSA eRNA knockdown, were studied using ChIP-seq. ChIP enriched DNA were sequenced using Illumina HiSeq 2500and input DNA were sequenced using Illumina HiSeq 2000.
2016-02-12 | E-GEOD-71704 | biostudies-arrayexpress
Project description:Castration resistant prostate cancer (CRPC) is a lethal disease. Sustained aberrant activation of androgen receptor (AR) becomes a central mechanism that contributes to endocrine therapy resistance. Here, we demonstrate that AR-bound enhancer RNAs (AR-eRNAs), including eRNA of the KLK3 (or PSA) gene, are upregulated in human CRPC cells and patient tissues. By enhancing C-termine domain (CTD) serine-2 phosphorylation of RNA polymerase II (Pol II-Ser2p), PSA eRNA acts in cis to promote PSA mRNA transcription and in trans to induce mRNA expression of a large set of genes involved in androgen action, cell cycle progression and tumorgenesis. Accordingly, we demonstrate that PSA eRNA binds in vitro and in vivo to CYCLIN T1, a regulatory subunit of the positive transcription elongation factor b (P-TEFb) complex that mediates Pol II-Ser2p. To identify the PSA eRNA’s functions on the Pol II-Ser2p and CYCLINT1 in the CRPC C4-2 cells, we detected the Pol II-Ser2p and CYCLINT1 ChIP-seq with or without PSA eRNA knockdown in the C4-2 cells. Moreover, to rule out the AR binding changes and identify the AR binding sites around the new genes, we detected the AR ChIP-seq in LNCaP and C4-2 cells with or without the androgen.
2016-02-12 | GSE65066 | GEO
Project description:RNAP II is frequently paused near gene promoters in mammals and its transition to productive elongation requires active recruitment of P-TEFb, a cyclin-dependent kinase for RNAP II and other key transcription elongation factors. A fraction of P-TEFb is sequestered in an inhibitory complex containing the 7SK noncoding RNA, but it has been unclear how P-TEFb is switched from the 7SK complex to RNAP II during transcription activation. We report that SRSF2 (also known as SC35, an SR splicing factor) is part of the 7SK complex assembled at gene promoters and plays a direct role in transcription pause release. We demonstrate RNA-dependent, coordinated release of SRSF2 and P-TEFb from the 7SK complex and transcription activation via SRSF2 binding to promoter-associated nascent RNA. These findings reveal an unanticipated SR protein function, a role for promoter-proximal nascent RNA in gene activation, and an analogous mechanism to HIV Tat/TAR for activating cellular genes. SR ChIP-seq, Pol II ChIP-seq, and Gro-seq
2013-05-09 | E-GEOD-45517 | biostudies-arrayexpress