Browse
Submit Data
Databases
API
Help

Dataset Information

0 Views

0 Connections

0 Citations

0 Reanalyses

0 Downloads

Omics score: 0

Nascent transcriptome changes in response to CDK12/13 inhibition in gliomas

ABSTRACT: To assess changes in the nascent and steady state transcriptomes after treatment with the CDK12/13 inhibitor THZ531, we performed SLAM-seq in the G7 glioblastoma derived cell line after DMSO treatment or treatment with 500 nM THZ531 for 6 hrs.

ORGANISM(S): Homo sapiens

PROVIDER: GSE186310 | GEO | 2026/01/29

REPOSITORIES: GEO

ACCESS DATA

Json Xml

Dataset's files

Source:

			Action	DRS
		Other

Items per page:

1 - 1 of 1

Similar Datasets

Genome-wide changes in RNAPII occupancy and phosphorylation in response to CDK12/13 inhibition in gliomas

Project description:To assess RNA Pol II (RNAPII) enrichment and modification state after treatment with the CDK12/13 inhibitor THZ531, we performed Cut&Run using antibodies against RNAPII as well as phosphorylated Serine 2 (S2P) or Serine 5 (S5P) in the c-terminal domain of RNAPII in the G7 glioblastoma derived cell line after DMSO treatment or treatment with THZ531 for 1 hr or 6 hrs. In addition, we performed Cut&Run of the H3K27me3 and H3K27Ac histone marks in untreated cells.

2026-01-29 | GSE186309 | GEO

MYC confers vulnerability to dual inhibition of CDK12 and CDK13 in high-risk Group 3 medulloblastoma

Project description:To investigate the effect of CDK12/13 inhibition and MYC over-expression on gene expression of high-risk Group 3 medulloblastoma cells, we established D341 cells treated or not with 100 nM THZ531 for 6 hours and silenced (siMYC) or not (siCtrl) for MYC expression for 48 hrs, respectively.

2023-09-13 | GSE225375 | GEO

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors [Affymetrix]

Project description:Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play critical roles in the regulation of gene transcription. However, the absence of CDK12 and CDK13 inhibitors has hindered the ability to investigate the consequences of their inhibition in healthy cells and cancer cells. Here we describe the rational design of a first-in-class CDK12 and CDK13 covalent inhibitor, THZ531. Co-crystallization of THZ531 with CDK12–cyclin K indicates that THZ531 irreversibly targets a cysteine located outside the kinase domain. THZ531 causes a loss of gene expression with concurrent loss of elongating and hyperphosphorylated RNA polymerase II. In particular, THZ531 substantially decreases the expression of DNA damage response genes and key super-enhancer-associated transcription factor genes. Coincident with transcriptional perturbation, THZ531 dramatically induced apoptotic cell death. Small molecules capable of specifically targeting CDK12 and CDK13 may thus help identify cancer subtypes that are particularly dependent on their kinase activities.

2016-08-29 | GSE72022 | GEO

Covalent targeting of remote cysteine residues to develop CDK12 and CDK13 inhibitors [ChIP-Seq]

2016-05-19 | GSE72023 | GEO

Quant-seq analysis to determine the effects of CDK12 and CDK13 inhibition by THZ531 in alternative polyadenylation

Project description:We performed 3' Quant-seq on MV4;11 cells after 6 hours treatment of THZ531 to determine whether CDK12 and CDK13 inhibtion cause alternative polyadenlation

2020-04-29 | GSE141368 | GEO

Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma [RNA-seq]

Project description:Anaplastic thyroid carcinoma (ATC) is the most aggressive type of thyroid cancer, with no effective treatment available. Identification of new anti-ATC drugs represents an urgent need. In this study, we find that ATC cells are highly sensitive to THZ531, a potent inhibitor of the transcriptional cyclin-dependent kinase (CDK), CDK12. Cell-based assays demonstrate that CDK12 inhibition significantly impedes cell cycle progression, induces apoptotic cell death, and impairs colony formation in ATC cells. THZ531 causes a loss of elongating RNA polymerase II and suppresses gene expression in ATC cells. An integrative analysis of gene expression profiles and super-enhancer landscape, combining with functional assays, leads to the discovery of two new ATC cancer genes, ZC3H4 and NEMP1. Furthermore, CDK12 inhibition enhances the sensitivity of ATC cells to doxorubicin-mediated chemotherapy. Thus, these findings indicate that CDK12 is a potential therapeutic target for ATC treatment and its inhibition may help to overcome the chemoresistance in patients with ATC

2022-09-19 | GSE137697 | GEO

Targeting CDK12-mediated transcription regulation in anaplastic thyroid carcinoma [ChIP-seq]

2022-09-19 | GSE137696 | GEO

Transcriptome wide alternative splicing analysis to determine the effect of CDK12 and CDK13 inhibition by THZ531 in alternative splicing (Total RNA-Seq)

Project description:We performed Total RNA-seq on MV4;11 cells after 6 hours treatment of THZ531 to determine whether CDK12 and CDK13 inhibtion to cause splicing defects.

2020-04-29 | GSE141372 | GEO

PolyA-sequencing in Jurkat cells upon CDK12 depletion.

Project description:We analyzed the 3' end of polyadenylated transcripts in Jurkat cells treated with either THZ531 (vs. DMSO) or the CDK12 degrader BSJ-4-116 (vs. BSJ-4-116NC).

2021-01-05 | GSE161650 | GEO

Development of an orally bioavailable CDK12/13 degrader and induction of synthetic lethality with AKT pathway inhibition [nascent]

Project description:Cyclin-dependent kinases 12 and 13 (CDK12 and CDK13) play pivotal roles in orchestrating transcription elongation, DNA damage response, and maintenance of genomic stability. Aberrant CDK12 expression, homozygous loss, and mutations have been documented in various malignancies. Previous studies have demonstrated CDK12 and 13 are promising therapeutic targets in cancer. In this study, we developed a selective CDK12/13 PROTAC degrader YJ9069, which in a panel of cancer cell lines, affirm its effectiveness in inhibiting cell proliferation in subsets of cancer. CDK12/13 degradation rapidly triggers gene-length dependent transcriptional elongation defects, leading to DNA damage and cell cycle arrest. In vivo, YJ9069 significantly suppresses tumor growth in prostate cancer cell line-derived xenograft (CDX) and patient-derived xenograft (PDX) models. Modifications of YJ9069 yielded a first-in-class orally bioavailable CDK12/13 degrader, YJ1206, which exhibits a comparable efficacy with significantly less toxicity. To identify pathways that may be synthetically lethal upon CDK12/13 degradation, we screened phosphorylation pathway arrays employing cell lines treated with YJ1206. Interestingly, degradation or genetic knock-down of CDK12/13, led to activation of the Akt pathway. Degradation of CDK12/13 with YJ1206, combined with AKT pathway inhibition with uprosertib, led to a striking synthetic lethal effect in pre-clinical models of prostate cancer. Taken together, these studies demonstrate that combination CDK12/13 and AKT pathway antagonism induces drug-drug synthetic lethality.

2024-08-14 | GSE262120 | GEO

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