Inferring the transcriptional regulatory mechanism of signal‐dependent gene expression via an integrative computational approach. Issue 10 (29th February 2020)

• Record Type: Journal Article
• Authors: Chiang, Sufeng; Shinohara, Hisaaki; Huang, Jia‐Hsin; Tsai, Huai‐Kuang; Okada, Mariko
• Is Part Of: FEBS letters. Volume 594:Issue 10(2020)
• Page Start: 1477
• Page End: 1496
• Publication Date: 2020-02-29
• Subjects: combinatorial control -- kinetic modeling -- regression analysis -- signal transduction -- transcriptional regulation -- transcription factor; Biochemistry -- Periodicals; Biophysics -- Periodicals; Molecular biology -- Periodicals; Biochimie -- Périodiques; Biochemistry; Biophysics; Molecular biology; Periodicals; 572.05
• DOI: 10.1002/1873-3468.13757
• Languages: English
• ISSNs: 0014-5793

Abstract

Abstract : Eukaryotic transcription factors (TFs) coordinate different upstream signals to regulate the expression of their target genes. To unveil this regulatory network in B‐cell receptor signaling, we developed a computational pipeline to systematically analyze the extracellular signal‐regulated kinase (ERK)‐ and IκB kinase (IKK)‐dependent transcriptome responses. We combined a bilinear regression method and kinetic modeling to identify the signal‐to‐TF and TF‐to‐gene dynamics, respectively. We input a set of time‐course experimental data for B cells and concentrated on transcriptional activators. The results show that the combination of TFs differentially controlled by ERK and IKK could contribute divergent expression dynamics in orchestrating the B‐cell response. Our findings provide insights into the regulatory mechanisms underlying signal‐dependent gene expression in eukaryotic cells. Abstract :