PMID- 33060136
OWN - NLM
STAT- MEDLINE
DCOM- 20210610
LR  - 20210611
IS  - 1549-5477 (Electronic)
IS  - 0890-9369 (Print)
IS  - 0890-9369 (Linking)
VI  - 34
IP  - 21-22
DP  - 2020 Nov 1
TI  - The transcription factor EGR2 is the molecular linchpin connecting STAT6 
      activation to the late, stable epigenomic program of alternative macrophage 
      polarization.
PG  - 1474-1492
LID - 10.1101/gad.343038.120 [doi]
AB  - Macrophages polarize into functionally distinct subtypes while responding to 
      microenvironmental cues. The identity of proximal transcription factors (TFs) 
      downstream from the polarization signals are known, but their activity is 
      typically transient, failing to explain the long-term, stable epigenomic programs 
      developed. Here, we mapped the early and late epigenomic changes of interleukin-4 
      (IL-4)-induced alternative macrophage polarization. We identified the TF, early 
      growth response 2 (EGR2), bridging the early transient and late stable gene 
      expression program of polarization. EGR2 is a direct target of IL-4-activated 
      STAT6, having broad action indispensable for 77% of the induced gene signature of 
      alternative polarization, including its autoregulation and a robust, downstream 
      TF cascade involving PPARG. Mechanistically, EGR2 binding results in chromatin 
      opening and the recruitment of chromatin remodelers and RNA polymerase II. Egr2 
      induction is evolutionarily conserved during alternative polarization of mouse 
      and human macrophages. In the context of tissue resident macrophages, Egr2 
      expression is most prominent in the lung of a variety of species. Thus, EGR2 is 
      an example of an essential and evolutionarily conserved broad acting factor, 
      linking transient polarization signals to stable epigenomic and transcriptional 
      changes in macrophages.
CI  - (c) 2020 Daniel et al.; Published by Cold Spring Harbor Laboratory Press.
FAU - Daniel, Bence
AU  - Daniel B
AD  - Department of Medicine, Johns Hopkins University School of Medicine, St. 
      Petersburg, Florida 33701, USA.
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      St. Petersburg, Florida 33701, USA.
AD  - Institute for Fundamental Biomedical Research, Johns Hopkins All Children's 
      Hospital, St. Petersburg, Florida 33701, USA.
FAU - Czimmerer, Zsolt
AU  - Czimmerer Z
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Halasz, Laszlo
AU  - Halasz L
AD  - Department of Medicine, Johns Hopkins University School of Medicine, St. 
      Petersburg, Florida 33701, USA.
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      St. Petersburg, Florida 33701, USA.
AD  - Institute for Fundamental Biomedical Research, Johns Hopkins All Children's 
      Hospital, St. Petersburg, Florida 33701, USA.
FAU - Boto, Pal
AU  - Boto P
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Kolostyak, Zsuzsanna
AU  - Kolostyak Z
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Poliska, Szilard
AU  - Poliska S
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Berger, Wilhelm K
AU  - Berger WK
AD  - Department of Medicine, Johns Hopkins University School of Medicine, St. 
      Petersburg, Florida 33701, USA.
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      St. Petersburg, Florida 33701, USA.
AD  - Institute for Fundamental Biomedical Research, Johns Hopkins All Children's 
      Hospital, St. Petersburg, Florida 33701, USA.
FAU - Tzerpos, Petros
AU  - Tzerpos P
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Nagy, Gergely
AU  - Nagy G
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Horvath, Attila
AU  - Horvath A
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Hajas, Gyorgy
AU  - Hajas G
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen 
      4032, Hungary.
FAU - Cseh, Timea
AU  - Cseh T
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Nagy, Aniko
AU  - Nagy A
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Sauer, Sascha
AU  - Sauer S
AD  - Otto Warburg Laboratory, Max Planck Institute for Molecular Genetics, Berlin 
      14195, Germany.
AD  - CU Systems Medicine, University of Wurzburg, Wurzburg 97070, Germany.
AD  - Berlin Institute for Medical Systems Biology, Max-Delbruck-Center for Molecular 
      Medicine, Berlin 13125, Germany.
AD  - Berlin Institute of Health, Max-Delbruck-Center for Molecular Medicine, Berlin 
      13125, Germany.
FAU - Francois-Deleuze, Jean
AU  - Francois-Deleuze J
AD  - Centre National de Genotypage, Institut de Genomique, Commissariat a l'Energie 
      Atomique, Evry 91000, France.
FAU - Szatmari, Istvan
AU  - Szatmari I
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
FAU - Bacsi, Attila
AU  - Bacsi A
AD  - Department of Immunology, Faculty of Medicine, University of Debrecen, Debrecen 
      4032, Hungary.
FAU - Nagy, Laszlo
AU  - Nagy L
AD  - Department of Medicine, Johns Hopkins University School of Medicine, St. 
      Petersburg, Florida 33701, USA.
AD  - Department of Biological Chemistry, Johns Hopkins University School of Medicine, 
      St. Petersburg, Florida 33701, USA.
AD  - Institute for Fundamental Biomedical Research, Johns Hopkins All Children's 
      Hospital, St. Petersburg, Florida 33701, USA.
AD  - Department of Biochemistry and Molecular Biology, Faculty of Medicine, University 
      of Debrecen, Debrecen 4032, Hungary.
LA  - eng
GR  - R01 DK115924/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, N.I.H., Extramural
PT  - Research Support, Non-U.S. Gov't
DEP - 20201015
PL  - United States
TA  - Genes Dev
JT  - Genes & development
JID - 8711660
RN  - 0 (Early Growth Response Protein 2)
RN  - 0 (Egr2 protein, mouse)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
CIN - Genes Dev. 2020 Nov 1;34(21-22):1407-1409. PMID: 33872194
MH  - Animals
MH  - Cell Polarity/*genetics
MH  - Chromosome Mapping
MH  - Conserved Sequence
MH  - Early Growth Response Protein 2/*genetics/*metabolism
MH  - Enhancer Elements, Genetic/genetics
MH  - Epigenesis, Genetic/*genetics
MH  - Gene Expression Regulation/genetics
MH  - Genome/genetics
MH  - Humans
MH  - Interleukin-4/metabolism
MH  - Macrophages/*cytology/physiology
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Interaction Domains and Motifs/genetics
MH  - STAT6 Transcription Factor/genetics/*metabolism
MH  - Transcriptional Activation/*genetics
MH  - Transcriptome/genetics
PMC - PMC7608752
OTO - NOTNLM
OT  - EGR2
OT  - IL-4
OT  - epigenomic regulation
OT  - macrophage polarization
OT  - transcription factor network
EDAT- 2020/10/17 06:00
MHDA- 2021/06/11 06:00
PMCR- 2021/05/01
CRDT- 2020/10/16 05:39
PHST- 2020/07/28 00:00 [received]
PHST- 2020/09/11 00:00 [accepted]
PHST- 2020/10/17 06:00 [pubmed]
PHST- 2021/06/11 06:00 [medline]
PHST- 2020/10/16 05:39 [entrez]
PHST- 2021/05/01 00:00 [pmc-release]
AID - gad.343038.120 [pii]
AID - 10.1101/gad.343038.120 [doi]
PST - ppublish
SO  - Genes Dev. 2020 Nov 1;34(21-22):1474-1492. doi: 10.1101/gad.343038.120. Epub 2020 
      Oct 15.