TY - JOUR
T1 - Redefining the transcriptional regulatory dynamics of classically and alternatively activated macrophages by deepCAGE transcriptomics
AU - Roy, Sugata
AU - Schmeier, Sebastian
AU - Arner, Erik
AU - Alam, Tanvir
AU - Parihar, Suraj P.
AU - Ozturk, Mumin
AU - Tamgue, Ousman
AU - Kawaji, Hideya
AU - De Hoon, Michiel J.L.
AU - Itoh, Masayoshi
AU - Lassmann, Timo
AU - Carninci, Piero
AU - Hayashizaki, Yoshihide
AU - Forrest, Alistair R.R.
AU - Bajic, Vladimir B.
AU - Guler, Reto
AU - Brombacher, Frank
AU - Suzuki, Harukazu
N1 - Publisher Copyright:
© The Author(s) 2015. Published by Oxford University Press on behalf of Nucleic Acids Research.
PY - 2015/8/18
Y1 - 2015/8/18
N2 - 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 andmore sustainable up-regulation inM2. 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 noncoding 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.
AB - 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 andmore sustainable up-regulation inM2. 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 noncoding 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.
UR - http://www.scopus.com/inward/record.url?scp=84944471180&partnerID=8YFLogxK
U2 - 10.1093/nar/gkv646
DO - 10.1093/nar/gkv646
M3 - Article
C2 - 26117544
AN - SCOPUS:84944471180
SN - 0305-1048
VL - 43
SP - 6969
EP - 6982
JO - Nucleic Acids Research
JF - Nucleic Acids Research
IS - 14
ER -