Inferring the transcriptional regulatory mechanism of signal-dependent gene expression via an integrative computational approach
© 2020 Federation of European Biochemical Societies..
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2020 |
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| Erschienen: |
2020 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:594 |
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| Enthalten in: |
FEBS letters - 594(2020), 10 vom: 20. Mai, Seite 1477-1496 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Chiang, Sufeng [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 05.05.2021 Date Revised 05.05.2021 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1002/1873-3468.13757 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM306467240 |
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| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a © 2020 Federation of European Biochemical Societies. | ||
| 520 | |a 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 | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a combinatorial control | |
| 650 | 4 | |a kinetic modeling | |
| 650 | 4 | |a regression analysis | |
| 650 | 4 | |a signal transduction | |
| 650 | 4 | |a transcription factor | |
| 650 | 4 | |a transcriptional regulation | |
| 650 | 7 | |a Receptors, Antigen, B-Cell |2 NLM | |
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| 650 | 7 | |a EC 2.7.11.10 |2 NLM | |
| 650 | 7 | |a Extracellular Signal-Regulated MAP Kinases |2 NLM | |
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| 700 | 1 | |a Shinohara, Hisaaki |e verfasserin |4 aut | |
| 700 | 1 | |a Huang, Jia-Hsin |e verfasserin |4 aut | |
| 700 | 1 | |a Tsai, Huai-Kuang |e verfasserin |4 aut | |
| 700 | 1 | |a Okada, Mariko |e verfasserin |4 aut | |
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