Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation

Handle URI:
http://hdl.handle.net/10754/325239
Title:
Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation
Authors:
Schmeier, Sebastian; MacPherson, Cameron R; Essack, Magbubah ( 0000-0003-2709-5356 ) ; Kaur, Mandeep; Schaefer, Ulf; Suzuki, Harukazu; Hayashizaki, Yoshihide; Bajic, Vladimir B. ( 0000-0001-5435-4750 )
Abstract:
Background: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee BioMed Central Ltd.
KAUST Department:
Computational Bioscience Research Center (CBRC)
Citation:
Schmeier S, MacPherson CR, Essack M, Kaur M, Schaefer U, et al. (2009) Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation. BMC Genomics 10: 595. doi:10.1186/1471-2164-10-595.
Publisher:
BioMed Central
Journal:
BMC Genomics
Issue Date:
10-Dec-2009
DOI:
10.1186/1471-2164-10-595
PubMed ID:
20003307
PubMed Central ID:
PMC2797535
Type:
Article
ISSN:
14712164
Appears in Collections:
Articles; Computational Bioscience Research Center (CBRC)

Full metadata record

DC FieldValue Language
dc.contributor.authorSchmeier, Sebastianen
dc.contributor.authorMacPherson, Cameron Ren
dc.contributor.authorEssack, Magbubahen
dc.contributor.authorKaur, Mandeepen
dc.contributor.authorSchaefer, Ulfen
dc.contributor.authorSuzuki, Harukazuen
dc.contributor.authorHayashizaki, Yoshihideen
dc.contributor.authorBajic, Vladimir B.en
dc.date.accessioned2014-08-27T09:41:36Z-
dc.date.available2014-08-27T09:41:36Z-
dc.date.issued2009-12-10en
dc.identifier.citationSchmeier S, MacPherson CR, Essack M, Kaur M, Schaefer U, et al. (2009) Deciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiation. BMC Genomics 10: 595. doi:10.1186/1471-2164-10-595.en
dc.identifier.issn14712164en
dc.identifier.pmid20003307en
dc.identifier.doi10.1186/1471-2164-10-595en
dc.identifier.urihttp://hdl.handle.net/10754/325239en
dc.description.abstractBackground: Macrophages are immune cells involved in various biological processes including host defence, homeostasis, differentiation, and organogenesis. Disruption of macrophage biology has been linked to increased pathogen infection, inflammation and malignant diseases. Differential gene expression observed in monocytic differentiation is primarily regulated by interacting transcription factors (TFs). Current research suggests that microRNAs (miRNAs) degrade and repress translation of mRNA, but also may target genes involved in differentiation. We focus on getting insights into the transcriptional circuitry regulating miRNA genes expressed during monocytic differentiation. Results: We computationally analysed the transcriptional circuitry of miRNA genes during monocytic differentiation using in vitro time-course expression data for TFs and miRNAs. A set of TF?miRNA associations was derived from predicted TF binding sites in promoter regions of miRNA genes. Time-lagged expression correlation analysis was utilised to evaluate the TF?miRNA associations. Our analysis identified 12 TFs that potentially play a central role in regulating miRNAs throughout the differentiation process. Six of these 12 TFs (ATF2, E2F3, HOXA4, NFE2L1, SP3, and YY1) have not previously been described to be important for monocytic differentiation. The remaining six TFs are CEBPB, CREB1, ELK1, NFE2L2, RUNX1, and USF2. For several miRNAs (miR-21, miR-155, miR-424, and miR-17-92), we show how their inferred transcriptional regulation impacts monocytic differentiation. Conclusions: The study demonstrates that miRNAs and their transcriptional regulatory control are integral molecular mechanisms during differentiation. Furthermore, it is the first study to decipher on a large-scale, how miRNAs are controlled by TFs during human monocytic differentiation. Subsequently, we have identified 12 candidate key controllers of miRNAs during this differentiation process. 2009 Schmeier et al; licensee BioMed Central Ltd.en
dc.language.isoenen
dc.publisherBioMed Centralen
dc.rightsThis is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/2.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.en
dc.rights.urihttp://creativecommons.org/licenses/by/2.0en
dc.subjectactivating transcription factor 2en
dc.subjectCCAAT enhancer binding proteinen
dc.subjectcyclic AMP responsive element binding proteinen
dc.subjectmicroRNAen
dc.subjectmiR 155en
dc.subjectmiR 17 92en
dc.subjectmir 21en
dc.subjectmiR 424en
dc.subjecttranscription factoren
dc.subjecttranscription factor E2F3en
dc.subjecttranscription factor Elk 1en
dc.subjecttranscription factor HOXA4en
dc.subjecttranscription factor NFE2L1en
dc.subjecttranscription factor NFE2L2en
dc.subjecttranscription factor RUNX1en
dc.subjecttranscription factor Sp3en
dc.subjecttranscription factor YY1en
dc.subjectunclassified drugen
dc.subjectupstream stimulatory factor 2en
dc.subjectmicroRNAen
dc.subjecttranscription factoren
dc.subjectbinding siteen
dc.subjectcell differentiationen
dc.subjectgene expressionen
dc.subjectgenetic transcriptionen
dc.subjecthuman cellen
dc.subjectin vitro studyen
dc.subjectmicroarray analysisen
dc.subjectmolecular mechanicsen
dc.subjectmonocyteen
dc.subjectpromoter regionen
dc.subjecttranscription regulationen
dc.subjectcytologyen
dc.subjectgene expression regulationen
dc.subjectgeneticsen
dc.subjectimmunologyen
dc.subjectBinding Sitesen
dc.subjectCell Differentiationen
dc.subjectGene Expression Regulationen
dc.subjectMicroRNAsen
dc.subjectMonocytesen
dc.subjectPromoter Regions, Geneticen
dc.subjectTranscription Factorsen
dc.subjectTranscription, Geneticen
dc.titleDeciphering the transcriptional circuitry of microRNA genes expressed during human monocytic differentiationen
dc.typeArticleen
dc.contributor.departmentComputational Bioscience Research Center (CBRC)en
dc.identifier.journalBMC Genomicsen
dc.identifier.pmcidPMC2797535en
dc.eprint.versionPublisher's Version/PDFen
dc.contributor.institutionSouth African National Bioinformatics Institute, University of the Western Cape, Modderdam Road, Bellville, South Africaen
dc.contributor.institutionRIKEN Omics Science Center, RIKEN Yokohama Institute, 1-7-22 Suehiro-cho, Tsurumi-ku Yokohama, Kanagawa, 230-0045, Japanen
dc.contributor.affiliationKing Abdullah University of Science and Technology (KAUST)en
kaust.authorSchmeier, Sebastianen
kaust.authorKaur, Mandeepen
kaust.authorBajic, Vladimir B.en
kaust.authorSchaefer, Ulfen

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