Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.
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ABSTRACT:
SUBMITTER: Zhang H
PROVIDER: S-EPMC6247954 | biostudies-literature | 2018 Nov
REPOSITORIES: biostudies-literature
Publications
Targeting CDK9 Reactivates Epigenetically Silenced Genes in Cancer.
Zhang Hanghang H Pandey Somnath S Travers Meghan M Sun Hongxing H Morton George G Madzo Jozef J Chung Woonbok W Khowsathit Jittasak J Perez-Leal Oscar O Barrero Carlos A CA Merali Carmen C Okamoto Yasuyuki Y Sato Takahiro T Pan Joshua J Garriga Judit J Bhanu Natarajan V NV Simithy Johayra J Patel Bela B Huang Jian J Raynal Noël J-M NJ Garcia Benjamin A BA Jacobson Marlene A MA Kadoch Cigall C Merali Salim S Zhang Yi Y Childers Wayne W Abou-Gharbia Magid M Karanicolas John J Baylin Stephen B SB Zahnow Cynthia A CA Jelinek Jaroslav J Graña Xavier X Issa Jean-Pierre J JJ
Cell 20181025 5
Cyclin-dependent kinase 9 (CDK9) promotes transcriptional elongation through RNAPII pause release. We now report that CDK9 is also essential for maintaining gene silencing at heterochromatic loci. Through a live cell drug screen with genetic confirmation, we discovered that CDK9 inhibition reactivates epigenetically silenced genes in cancer, leading to restored tumor suppressor gene expression, cell differentiation, and activation of endogenous retrovirus genes. CDK9 inhibition dephosphorylates ...[more]
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