Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches
Copyright © 2017 Elsevier B.V. All rights reserved..
MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets. We investigated the LPS-induced expression changes at mature miRNA and pri-miRNA levels in mouse macrophages utilizing a small RNA-seq method and publicly available GRO-seq dataset, respectively. Next, we identified an enhancer set associated with LPS-responsive pri-miRNAs based on publicly available H3K4 mono-methylation-specific ChIP-seq and GRO-seq datasets. This enhancer set was further characterized by the combination of publicly available ChIP and ATAC-seq datasets. Finally, direct interactions between the miR-155-coding genomic region and its distal regulatory elements were identified using a 3C-seq approach. Our analysis revealed 15 robustly LPS-regulated miRNAs at the transcriptional level. In addition, we found that these miRNA genes are associated with an inflammation-responsive enhancer network. Based on NFκB-p65 and JunB transcription factor binding, we showed two distinct enhancer subsets associated with LPS-activated miRNAs that possess distinct epigenetic characteristics and LPS-responsiveness. Finally, our 3C-seq analysis revealed the LPS-induced extensive reorganization of the pri-miR-155-associated functional chromatin domain as well as chromatin loop formation between LPS-responsive enhancers and the promoter region. Our genomic approach successfully combines various genome-wide datasets and allows the identification of the putative regulatory elements controlling miRNA expression in classically activated macrophages.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2018 |
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| Erschienen: |
2018 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:1861 |
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| Enthalten in: |
Biochimica et biophysica acta. Gene regulatory mechanisms - 1861(2018), 1 vom: 15. Jan., Seite 14-28 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Czimmerer, Zsolt [VerfasserIn] |
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| Links: |
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| Anmerkungen: |
Date Completed 10.04.2018 Date Revised 19.09.2018 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1016/j.bbagrm.2017.11.003 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM277996686 |
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| 100 | 1 | |a Czimmerer, Zsolt |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Dynamic transcriptional control of macrophage miRNA signature via inflammation responsive enhancers revealed using a combination of next generation sequencing-based approaches |
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| 500 | |a Date Revised 19.09.2018 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright © 2017 Elsevier B.V. All rights reserved. | ||
| 520 | |a MicroRNAs are important components of the post-transcriptional fine-tuning of macrophage gene expression in physiological and pathological conditions. However, the mechanistic underpinnings and the cis-acting genomic factors of how macrophage polarizing signals induce miRNA expression changes are not well characterized. Therefore, we systematically evaluated the transcriptional basis underlying the inflammation-mediated regulation of macrophage microRNome using the combination of different next generation sequencing datasets. We investigated the LPS-induced expression changes at mature miRNA and pri-miRNA levels in mouse macrophages utilizing a small RNA-seq method and publicly available GRO-seq dataset, respectively. Next, we identified an enhancer set associated with LPS-responsive pri-miRNAs based on publicly available H3K4 mono-methylation-specific ChIP-seq and GRO-seq datasets. This enhancer set was further characterized by the combination of publicly available ChIP and ATAC-seq datasets. Finally, direct interactions between the miR-155-coding genomic region and its distal regulatory elements were identified using a 3C-seq approach. Our analysis revealed 15 robustly LPS-regulated miRNAs at the transcriptional level. In addition, we found that these miRNA genes are associated with an inflammation-responsive enhancer network. Based on NFκB-p65 and JunB transcription factor binding, we showed two distinct enhancer subsets associated with LPS-activated miRNAs that possess distinct epigenetic characteristics and LPS-responsiveness. Finally, our 3C-seq analysis revealed the LPS-induced extensive reorganization of the pri-miR-155-associated functional chromatin domain as well as chromatin loop formation between LPS-responsive enhancers and the promoter region. Our genomic approach successfully combines various genome-wide datasets and allows the identification of the putative regulatory elements controlling miRNA expression in classically activated macrophages | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Chromatin looping | |
| 650 | 4 | |a Enhancer | |
| 650 | 4 | |a Inflammation | |
| 650 | 4 | |a Macrophage | |
| 650 | 4 | |a pri-miRNA | |
| 650 | 7 | |a Chromatin |2 NLM | |
| 650 | 7 | |a Lipopolysaccharides |2 NLM | |
| 650 | 7 | |a MicroRNAs |2 NLM | |
| 650 | 7 | |a Mirn155 microRNA, mouse |2 NLM | |
| 650 | 7 | |a Rela protein, mouse |2 NLM | |
| 650 | 7 | |a Transcription Factor RelA |2 NLM | |
| 700 | 1 | |a Horvath, Attila |e verfasserin |4 aut | |
| 700 | 1 | |a Daniel, Bence |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, Gergely |e verfasserin |4 aut | |
| 700 | 1 | |a Cuaranta-Monroy, Ixchelt |e verfasserin |4 aut | |
| 700 | 1 | |a Kiss, Mate |e verfasserin |4 aut | |
| 700 | 1 | |a Kolostyak, Zsuzsanna |e verfasserin |4 aut | |
| 700 | 1 | |a Poliska, Szilard |e verfasserin |4 aut | |
| 700 | 1 | |a Steiner, Laszlo |e verfasserin |4 aut | |
| 700 | 1 | |a Giannakis, Nikolas |e verfasserin |4 aut | |
| 700 | 1 | |a Varga, Tamas |e verfasserin |4 aut | |
| 700 | 1 | |a Nagy, Laszlo |e verfasserin |4 aut | |
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| 856 | 4 | 0 | |u http://dx.doi.org/10.1016/j.bbagrm.2017.11.003 |3 Volltext |
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