Sequence dependency and regulatory function of dimeric NOTCH1/RBPJ complexes on coding and non-coding transcription in T-lymphoblastic leukemia

NOTCH/RBPJ/MAML ternary transcriptional complex binds to regulatory element and drives gene expression. The complex can function as monomer and dimer. How dimeric complexes regulate gene expression in human cancer is not well studied. Here, we integrate genomic data sets and analyze Notch dimeric complexes-regulated transcriptome and cis-regulatory elements. A subset of coding and non-coding RNA is Notch dimeric complexes-associated. Dimeric complexes recognition sequence enriched in functional dynamic Notch sites and majority of dimer recognition sequence located in (super-)enhancers. Overall design: Gene expression profiling for Notch-sensitive TLL cell lines using RNA-seq, with replicates

NOTCH/RBPJ/MAML 三元转录复合物（ternary transcriptional complex）结合调控元件并驱动基因表达。该复合物可通过单体或二聚体形式发挥功能。目前学界对二聚体形式的该复合物在人类癌症中调控基因表达的机制研究尚不充分。本研究整合多组基因组数据集，分析Notch二聚体复合物所调控的转录组与顺式调控元件（cis-regulatory elements）。部分编码RNA及非编码RNA与Notch二聚体复合物相关。二聚体复合物的识别序列显著富集于具有功能活性的动态Notch结合位点，且多数二聚体识别序列分布于（超级）增强子（super-enhancers）区域。实验整体设计：采用RNA测序（RNA-seq）技术对Notch敏感的TLL细胞系开展基因表达谱分析，且设置生物学重复。