Inferring the transcriptional regulatory mechanism of signal-dependent gene expression via an integrative computational approach

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 I$ąppa$B 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.

Publication
FEBS Letters
Sufeng Chiang
Sufeng Chiang
Senior Research Specialist
Jia-Hsin Huang
Jia-Hsin Huang
Assistant Professor
Huai-Kuang Tsai
Huai-Kuang Tsai
Research Fellow/Professor