4. CDK9抑制增加了BRD4与染色质的结合 BRD4是SE相关基因的正调控因子,该基因与超乙酰化组蛋白结合以招募CDK9,为了在基因组上进行定位,作者对BRD4和RNAPII进行了ChIP-Seq检测。用AZD4573处理淋巴瘤细胞8h,然后进行洗脱,发现BRD4和RNAPII信号在启动子区域迅速富集(图4.A),而且与单独的实验化合物相比,同时持续靶向BRD...
接下来作者分析CDK9抑制剂处理后P-TEFb在转录起始位点(TSS)占据的变化,发现CDK9抑制后P-TEFb的在转录起始位点募集受到显著抑制(图6B, C),这说明受到转录抑制的基因与P-TEFb调节密切相关;作者又分析T-bet相关的ChIP-seq数据库,再进行GSEA分析,...
在RNAPII暂停导致的最初转录抑制之后,研究者观察到包括MYC和PIM3在内的几个癌基因的转录恢复。ATAC-Seq和CHIP-Seq实验表明,CDK9i通过染色质可及性的双向改变诱导表观遗传重塑,抑制启动子的激活,并导致超级增强子景观的持续重新编程。CRISPR文库筛选表明,介体复合体中的SE相关基因以及AKT1对CDK9i具有抗性。 与此一致的...
研究人员考察了Int-PP2A复合物在稳态条件下控制RNAPII驱动的转录以及在急性促炎症和有丝分裂刺激的反应中的重要性。在THP-1细胞中进行的急性INTS6缺失60h后的ChIP-seq试验显示,整个TSS区和基因体的RNAPII占位增加,表明在无CDK9抑制的情况下,稳...
对THZ1处理后的两种亚型细胞进行RNA-seq和H3K27ac ChIP-seq联合分析发现与转录相关的基因在基底型PDAC细胞中受到有效和特异性抑制，此外，THZ1处理能显著抑制基底型PDAC的翻译。已知细胞可以通过ISR显著减少翻译以在各种压力下生存，他们发现所有基底型PDAC细胞系都具有较低的ISR激活以及相对较高的翻译率。那么经典型如何...
Using time‐resolved transcriptional profiling (SLAM‐seq), targeted proteomics, and ChIP‐seq, we show that, similar to viral infection, CDK9 inhibition significantly suppresses transcription of most genes but allows selective transcription and translation of cytokines related to the innate ...
(TSS ± 1 kb) where there was strong co-localization of AFF1 and HEXIM1 ChIP-seq signal (Fig.5c, d). We also performed CDK9 ChIP-seq using HA-tagged CDK9. We found that 93% of AFF1-HEXIM1 shared peaks overlap with CDK9 ChIP-seq peaks (Supplementary Fig.5a–c). These ...
Furthermore, Ser2-phosphorylated RNA PolII binding along the HOTAIR gene after CDK7 inhibition in cancer was analyzed by ChIP-seq. We found that inhibition of CDK7 decreased the RNA PolII Ser-2 phosphorylation along the HOTAIR gene (Figure S7G), which suggested that CDK7-CDK9 promotes ...
a, Correlation between ChIP–seq samples. Paired-end sequencing reads were mapped to the fission-yeast genome using Bowtie2 (Galaxy v.2.2.6.2). Mapped reads of each biological replicate were used to calculate correlation between pairs of replicates. Values in boxes represent Pearson’s correlation...
We reanalyzed our published bulk RNA-seq dataset as described previously [11]. The R package DESeq2 (version 1.30.1) was used to perform differential expression analysis [19]. Genes with adjusted p-value less than 0.05 and absolute value of log2 fold change greater than 1 were considered ...