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DOT1L-mediated CDK9 methylation is essential for DNA double-strand break repair

ABSTRACT: P-TEFb is a key regulator of transcription elongation and is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1. DOT1L is a histone H3K79 methyltransferase. Here, we show that treatment with the DOT1L inhibitor EPZ-5676 induces transcriptome changes in HCT116 cells. We further demonstrate that DOT1L methylates CDK9 at lysine 56 and that CDK9 methylation-deficient mutant K56A reshapes genome-wide CDK9 occupancy. Notably, changes in CDK9 occupancy are particularly pronounced at double-strand break (DSB)-related genes and are associated with the regulation of their transcription. This idataset includes RNA-seq and ChIP-seq data generated from HCT116 cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE314839 | GEO | 2025/12/29

REPOSITORIES: GEO

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DOT1L-mediated CDK9 methylation is essential for DNA double-strand break repair [RNA-seq]

Project description:P-TEFb is a key regulator of transcription elongation and is composed of cyclin-dependent kinase 9 (CDK9) and cyclin T1. DOT1L is a histone H3K79 methyltransferase. Here, we show that treatment with the DOT1L inhibitor EPZ-5676 induces transcriptome changes in HCT116 cells. We further demonstrate that DOT1L methylates CDK9 at lysine 56 and that CDK9 methylation-deficient mutant K56A reshapes genome-wide CDK9 occupancy. Notably, changes in CDK9 occupancy are particularly pronounced at double-strand break (DSB)-related genes and are associated with the regulation of their transcription. This idataset includes RNA-seq and ChIP-seq data generated from HCT116 cells.

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Transcriptome analyses by RNA-seq with NELFE knockdown and EPZ-5676 or HMBA treated HCT116 cells

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Project description:This study describes the transcriptome profiling of: 1) MM-401, a MLL1 specific inhibitor in MAF9 cells; 2) Comparation of the transcriptone profilings of MM-401,EPZ-5676 (Dot1L inhibitor), MI-2(Menin inhibitor) and iBET(Brd4 inhibitor) in MAF9 leukemia cells.

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A novel Menin-MLL inhibitor induces specific chromatin changes and eradicates disease in models of MLL-rearranged leukemia [RNA-seq]

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