Inferring the transcriptional regulatory mechanism of signal-dependent gene expression via an integrative computational approach.
FEBS Lett
; 594(10): 1477-1496, 2020 05.
Article
de En
| MEDLINE
| ID: mdl-32052437
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.
Mots clés
Texte intégral:
1
Collection:
01-internacional
Base de données:
MEDLINE
Sujet principal:
Transcription génétique
/
Simulation numérique
/
Transduction du signal
/
Régulation de l'expression des gènes
Type d'étude:
Prognostic_studies
Limites:
Animals
Langue:
En
Journal:
FEBS Lett
Année:
2020
Type de document:
Article
Pays d'affiliation:
Taïwan