Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics
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Type
ArticleAuthors
Roy, S.Schmeier, S.
Arner, E.
Alam, Tanvir

Parihar, S. P.
Ozturk, M.
Tamgue, O.
Kawaji, H.
de Hoon, M. J. L.
Itoh, M.
Lassmann, T.
Carninci, P.
Hayashizaki, Y.
Forrest, A. R. R.
Bajic, Vladimir B.

Guler, R.
Consortium, F.
Brombacher, F.
Suzuki, H.
KAUST Department
Computational Bioscience Research Center (CBRC)Computer, Electrical and Mathematical Sciences and Engineering (CEMSE) Division
Computer Science Program
Applied Mathematics and Computational Science Program
Date
2015-06-27Online Publication Date
2015-06-27Print Publication Date
2015-08-18Permanent link to this record
http://hdl.handle.net/10754/558766
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Show full item recordAbstract
Classically or alternatively activated macrophages (M1 and M2, respectively) play distinct and important roles for microbiocidal activity, regulation of inflammation and tissue homeostasis. Despite this, their transcriptional regulatory dynamics are poorly understood. Using promoter-level expression profiling by non-biased deepCAGE we have studied the transcriptional dynamics of classically and alternatively activated macrophages. Transcription factor (TF) binding motif activity analysis revealed four motifs, NFKB1_REL_RELA, IRF1,2, IRF7 and TBP that are commonly activated but have distinct activity dynamics in M1 and M2 activation. We observe matching changes in the expression profiles of the corresponding TFs and show that only a restricted set of TFs change expression. There is an overall drastic and transient up-regulation in M1 and a weaker and more sustainable up-regulation in M2. Novel TFs, such as Thap6, Maff, (M1) and Hivep1, Nfil3, Prdm1, (M2) among others, were suggested to be involved in the activation processes. Additionally, 52 (M1) and 67 (M2) novel differentially expressed genes and, for the first time, several differentially expressed long non-coding RNA (lncRNA) transcriptome markers were identified. In conclusion, the finding of novel motifs, TFs and protein-coding and lncRNA genes is an important step forward to fully understand the transcriptional machinery of macrophage activation.Citation
Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics 2015 Nucleic Acids ResearchPublisher
Oxford University Press (OUP)Journal
Nucleic Acids ResearchPubMed ID
26117544Additional Links
http://nar.oxfordjournals.org/lookup/doi/10.1093/nar/gkv646ae974a485f413a2113503eed53cd6c53
10.1093/nar/gkv646
Scopus Count
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