Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics

S. Roy, S. Schmeier, E. Arner, Tanvir Alam, S. P. Parihar, M. Ozturk, O. Tamgue, H. Kawaji, M. J. L. de Hoon, M. Itoh, T. Lassmann, P. Carninci, Y. Hayashizaki, A. R. R. Forrest, Vladimir B. Bajic, R. Guler, F. Consortium, F. Brombacher, H. Suzuki

Research output: Contribution to journalArticlepeer-review

35 Scopus citations

Abstract

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.
Original languageEnglish (US)
Pages (from-to)6969-6982
Number of pages14
JournalNucleic Acids Research
Volume43
Issue number14
DOIs
StatePublished - Jun 27 2015

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