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

ABSTRACT: 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

ORGANISM(S): Homo sapiens

PROVIDER: GSE141368 | GEO | 2020/04/29

REPOSITORIES: GEO

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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.

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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.

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

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Project description:We used 3' RNA-Seq to determine the effects of slow elongating Pol II on polyadenatltion site usages, also the effects of CDK12 and CDK13 inhibition caused by THZ531 on alternative polyadenylation

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

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

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Quant-seq analysis of differential gene expression and polyadenylation site usages in caused by inhibition of CDK12 and CDK13 using THZ531 in THP-1 cells (3’ Quant-seq)

Project description:We used 3' RNA-Seq to determine effect of dual inhibition of CDK12 and CDK13 on gene expression and polyadenatltion site usages in THP-1 cells

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CDK12 and CDK13

Project description:CDK12 and CDK13

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Transcriptome wide analysis of differential gene expression and polyadenylation site usages caused by inhibition of CDK12 and/or CDK13 in MV4;11 cells (3’ Quant-seq)

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