PMID- 23398888
OWN - NLM
STAT- MEDLINE
DCOM- 20130906
LR  - 20231104
IS  - 1471-2164 (Electronic)
IS  - 1471-2164 (Linking)
VI  - 14
DP  - 2013 Feb 11
TI  - Combined ChIP-Seq and transcriptome analysis identifies AP-1/JunD as a primary 
      regulator of oxidative stress and IL-1beta synthesis in macrophages.
PG  - 92
LID - 10.1186/1471-2164-14-92 [doi]
AB  - BACKGROUND: The oxidative burst is one of the major antimicrobial mechanisms 
      adopted by macrophages. The WKY rat strain is uniquely susceptible to 
      experimentally induced macrophage-dependent crescentic glomerulonephritis (Crgn). 
      We previously identified the AP-1 transcription factor JunD as a determinant of 
      macrophage activation in WKY bone marrow-derived macrophages (BMDMs). JunD is 
      over-expressed in WKY BMDMs and its silencing reduces Fc receptor-mediated 
      oxidative burst in these cells. RESULTS: Here we combined Jund RNA interference 
      with microarray analyses alongside ChIP-sequencing (ChIP-Seq) analyses in WKY 
      BMDMs to investigate JunD-mediated control of macrophage activation in basal and 
      lipopolysaccharide (LPS) stimulated cells. Microarray analysis following Jund 
      silencing showed that Jund activates and represses gene expression with marked 
      differential expression (>3 fold) for genes linked with oxidative stress and 
      IL-1beta expression. These results were complemented by comparing whole genome 
      expression in WKY BMDMs with Jund congenic strain (WKY.LCrgn2) BMDMs which 
      express lower levels of JunD. ChIP-Seq analyses demonstrated that the increased 
      expression of JunD resulted in an increased number of binding events in WKY BMDMs 
      compared to WKY.LCrgn2 BMDMs. Combined ChIP-Seq and microarray analysis revealed 
      a set of primary JunD-targets through which JunD exerts its effect on oxidative 
      stress and IL-1beta synthesis in basal and LPS-stimulated macrophages. CONCLUSIONS: 
      These findings demonstrate how genetically determined levels of a transcription 
      factor affect its binding sites in primary cells and identify JunD as a key 
      regulator of oxidative stress and IL-1beta synthesis in primary macrophages, which 
      may play a role in susceptibility to Crgn.
FAU - Hull, Richard P
AU  - Hull RP
AD  - MRC Clinical Sciences Centre, Imperial College London, Hammersmithhospital, Du 
      Cane Road W12 0NN, London, UK.
FAU - Srivastava, Prashant K
AU  - Srivastava PK
FAU - D'Souza, Zelpha
AU  - D'Souza Z
FAU - Atanur, Santosh S
AU  - Atanur SS
FAU - Mechta-Grigoriou, Fatima
AU  - Mechta-Grigoriou F
FAU - Game, Laurence
AU  - Game L
FAU - Petretto, Enrico
AU  - Petretto E
FAU - Cook, H Terence
AU  - Cook HT
FAU - Aitman, Timothy J
AU  - Aitman TJ
FAU - Behmoaras, Jacques
AU  - Behmoaras J
LA  - eng
GR  - MC_U120097112/MRC_/Medical Research Council/United Kingdom
GR  - WT092523MA/WT_/Wellcome Trust/United Kingdom
GR  - 087182/Z/08/Z/WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130211
PL  - England
TA  - BMC Genomics
JT  - BMC genomics
JID - 100965258
RN  - 0 (Interleukin-1beta)
RN  - 0 (JunD protein, rat)
RN  - 0 (Lipopolysaccharides)
RN  - 0 (Proto-Oncogene Proteins c-jun)
RN  - 0 (Transcription Factor AP-1)
SB  - IM
MH  - Animals
MH  - Binding Sites
MH  - Gene Expression/drug effects
MH  - Gene Expression Profiling
MH  - Glomerulonephritis/chemically induced/genetics/metabolism/pathology
MH  - Interleukin-1beta/biosynthesis/genetics/*metabolism
MH  - Lipopolysaccharides/toxicity
MH  - Macrophages/cytology/drug effects/*metabolism
MH  - Oxidative Stress/*genetics
MH  - Primary Cell Culture
MH  - Protein Binding
MH  - *Proto-Oncogene Proteins c-jun/genetics/metabolism
MH  - Rats
MH  - *Transcription Factor AP-1/genetics/metabolism
PMC - PMC3608227
EDAT- 2013/02/13 06:00
MHDA- 2013/09/07 06:00
PMCR- 2013/02/11
CRDT- 2013/02/13 06:00
PHST- 2012/10/13 00:00 [received]
PHST- 2013/02/01 00:00 [accepted]
PHST- 2013/02/13 06:00 [entrez]
PHST- 2013/02/13 06:00 [pubmed]
PHST- 2013/09/07 06:00 [medline]
PHST- 2013/02/11 00:00 [pmc-release]
AID - 1471-2164-14-92 [pii]
AID - 10.1186/1471-2164-14-92 [doi]
PST - epublish
SO  - BMC Genomics. 2013 Feb 11;14:92. doi: 10.1186/1471-2164-14-92.