Inhibition of gene transcription after THZ1 treatment in HeLa
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ABSTRACT:
PROVIDER: PRJNA516711 | ENA |
REPOSITORIES: ENA
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Project description:ChIP-seq analysis was performed in an adult T-cell leukemia/lymphoma cell line (TL-Om1) to analyze DNA bindings of RNA polymerase II (Pol II) after treatment with the THZ1 CDK7 inhibitor.
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Project description:Purpose: To assess THZ1-induced global changes of transcriptome of Hh-driven cancer Methods: SMB56 or SMB56-shSufu cells were mouse hedgehog-driven medulloblastoma cell lines that are either responsive or resistant to SMO inhibitor (GDC-0449). They were treated with 0.1 uM THZ1 or DMSO for 8 hours. 1 uM GDC-0449 treated SMB56 cells were included as control. Gene expression profiles were generated by RNAseq, in duplicate, using Hiseq3000. The RNAseq reads were mapped to the hg19 reference genome using STAR (v2.5.3a). Expression levels for each sample were quantified to FPKM using Cufflinks (v2.2.1). Differential expression analysis was carried out using R package DESeq2 (v1.20.0) Results: Compared to GDC-0449 treatment in SMB56 cells, THZ1 induced a robust global transcriptional downregulation in both SMB56 and SMB56-shSufu cells. When we compared the top 2000 significantly downregulated genes between THZ1-treated SMB56 and SMB56-shSufu cells, we found they had ~70% in common. GSEA reveals Hh-target genes are enriched in DMSO treated cells versus THZ1-treated ones. Conclusions: CDK7 inhibition induced a robust and similar transcriptional downregulation in both SMB56 and SMB56-shSufu cells, with preferential targeting of Hh pathway transcriptional output.
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