Format

Send to

Choose Destination
Nucleic Acids Res. 2015 Aug 18;43(14):6969-82. doi: 10.1093/nar/gkv646. Epub 2015 Jun 27.

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

Author information

1
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
2
Massey University, Institute of Natural and Mathematical Sciences, Auckland, New Zealand.
3
King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Thuwal, Saudi Arabia.
4
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africa University of Cape Town, Health Science Faculty, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, Cape Town, South Africa.
5
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Preventive Medicine and Diagnosis Innovation Program (PMI), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
6
Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Preventive Medicine and Diagnosis Innovation Program (PMI), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
7
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Massey University, Institute of Natural and Mathematical Sciences, Auckland, New Zealand King Abdullah University of Science and Technology (KAUST), Computational Bioscience Research Center (CBRC), Computer, Electrical and Mathematical Sciences and Engineering Division (CEMSE), Thuwal, Saudi Arabia International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africa University of Cape Town, Health Science Faculty, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, Cape Town, South Africa Riken Preventive Medicine and Diagnosis Innovation Program (PMI), 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan.
8
International Centre for Genetic Engineering and Biotechnology (ICGEB), Cape Town Component, Cape Town, South Africa University of Cape Town, Health Science Faculty, Institute of Infectious Diseases and Molecular Medicine (IDM), Division of Immunology, Cape Town, South Africa harukazu@gsc.riken.jp.
9
Division of Genomic Technologies, RIKEN Center for Life Science Technologies, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan Riken Omics Science Center, 1-7-22 Suehiro-cho, Tsurumi-ku, Yokohama 230-0045, Japan harukazu@gsc.riken.jp.

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.

PMID:
26117544
PMCID:
PMC4538831
DOI:
10.1093/nar/gkv646
[Indexed for MEDLINE]
Free PMC Article

Supplemental Content

Full text links

Icon for Silverchair Information Systems Icon for PubMed Central
Loading ...
Support Center