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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression

ABSTRACT: This SuperSeries is composed of the SubSeries listed below.

ORGANISM(S): Homo sapiens

PROVIDER: GSE120072 | GEO | 2019/07/22

REPOSITORIES: GEO

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq)

Project description:In this study we characterized the importance of CDK12-kinase activity in cell cycle regulation, using CDK12 anolog-sentive cells. Inhibition of analog-sensitive CDK12 reveals its catalytic activity is necessary for optimal G1/S progression. Mechanistically, CDK12 regulates transcription of core DNA replication genes and affects timely assembly of pre-replication DNA complex on chromatin. We have performed 3’-end RNA-sequencing after CDK12 inhibition and identified that the expression of core DNA replication genes were affected. To investigate further, we carried out nuclear RNA-seq coupled with ChIP-seq, and demonstrated that CDK12 regulates RNAPII processivity of core DNA replication genes and optimal G1/S progression.

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (nuclear RNA)

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (3' RNA)

2019-07-22 | GSE120070 | GEO

CDK12 controls G1/S progression by regulating RNAPII processivity at core DNA replication genes.

Project description:CDK12 is a kinase associated with elongating RNA polymerase II (RNAPII) and is frequently mutated in cancer. CDK12 depletion reduces the expression of homologous recombination (HR) DNA repair genes, but comprehensive insight into its target genes and cellular processes is lacking. We use a chemical genetic approach to inhibit analog-sensitive CDK12, and find that CDK12 kinase activity is required for transcription of core DNA replication genes and thus for G1/S progression. RNA-seq and ChIP-seq reveal that CDK12 inhibition triggers an RNAPII processivity defect characterized by a loss of mapped reads from 3'ends of predominantly long, poly(A)-signal-rich genes. CDK12 inhibition does not globally reduce levels of RNAPII-Ser2 phosphorylation. However, individual CDK12-dependent genes show a shift of P-Ser2 peaks into the gene body approximately to the positions where RNAPII occupancy and transcription were lost. Thus, CDK12 catalytic activity represents a novel link between regulation of transcription and cell cycle progression. We propose that DNA replication and HR DNA repair defects as a consequence of CDK12 inactivation underlie the genome instability phenotype observed in many cancers.

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq II)

2019-07-22 | GSE130509 | GEO

CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression

Project description:CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (nuclear RNA)

Project description:CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (nuclear RNA)

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (3' RNA)

Project description:CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (3' RNA)

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq)

Project description:CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq)

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CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq II)

Project description:CDK12 catalytic activity is rate-limiting for RNAPII processivity on core DNA replication genes and G1/S progression (ChIP-Seq II)

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