PMID- 17623651
OWN - NLM
STAT- MEDLINE
DCOM- 20071019
LR  - 20220129
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 282
IP  - 37
DP  - 2007 Sep 14
TI  - Transcription factor PU.1 controls transcription start site positioning and 
      alternative TLR4 promoter usage.
PG  - 26874-26883
LID - S0021-9258(20)58758-9 [pii]
LID - 10.1074/jbc.M703856200 [doi]
AB  - Human and mouse show markedly different sensitivities toward bacterial 
      endotoxins, and recent evidence suggests that a species-specific regulation of 
      the lipopolysaccharide receptor Toll-like receptor 4 (Tlr4) may contribute to 
      this phenomenon. To gain further insight into mechanisms of Tlr4 regulation, we 
      conducted a detailed in vivo and in vitro study of the murine Tlr4 gene, 
      including analysis of transcription start site location, transcription factor 
      occupancy, and activities of its proximal regulatory sequences. Our analyses 
      identified a PU.1-dependent myeloid promoter, which is conserved between humans 
      and mouse. We also identified an additional, distal promoter, located 
      approximately 200 bp upstream of the myeloid-specific promoter, which is a 
      functional target of E-box binding factors. In contrast to humans, where 
      non-myeloid cells utilize both promoters, the distal Tlr4 promoter initiates all 
      Tlr4 transcripts in murine non-myeloid cells, indicating that species-specific 
      differences in TLR4 mRNA regulation may primarily exist in non-myeloid cell 
      types. Interestingly, PU.1 null murine myeloid progenitor cells predominantly use 
      the distal promoter, and the conditional induction of PU.1 expression in these 
      cells leads to the rapid switch of transcription initiation to the proximal 
      myeloid promoter. This indicates a direct role for PU.1 in determining the 
      transcriptional start site and in recruiting the basal transcription machinery to 
      myeloid promoters.
FAU - Lichtinger, Monika
AU  - Lichtinger M
AD  - Department of Hematology and Oncology, University of Regensburg Medical School, 
      93042 Regensburg, Germany.
FAU - Ingram, Richard
AU  - Ingram R
AD  - Section of Experimental Haematology, University of Leeds, St James's University 
      Hospital, Leeds LS9 7TF, United Kingdom.
FAU - Hornef, Mathias
AU  - Hornef M
AD  - Department for Medical Microbiology and Hygiene, University Clinic of Freiburg, 
      79104 Freiburg, Germany.
FAU - Bonifer, Constanze
AU  - Bonifer C
AD  - Section of Experimental Haematology, University of Leeds, St James's University 
      Hospital, Leeds LS9 7TF, United Kingdom.
FAU - Rehli, Michael
AU  - Rehli M
AD  - Department of Hematology and Oncology, University of Regensburg Medical School, 
      93042 Regensburg, Germany. Electronic address: 
      michael.rehli@klinik.uni-regensburg.de.
LA  - eng
GR  - BBS/B/07438/BB_/Biotechnology and Biological Sciences Research Council/United 
      Kingdom
GR  - WT_/Wellcome Trust/United Kingdom
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20070710
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Tlr4 protein, mouse)
RN  - 0 (Toll-Like Receptor 4)
RN  - 0 (Trans-Activators)
RN  - 0 (proto-oncogene protein Spi-1)
SB  - IM
MH  - Animals
MH  - Base Sequence
MH  - Humans
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Mice, Inbred C57BL
MH  - Molecular Sequence Data
MH  - *Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*physiology
MH  - Species Specificity
MH  - Toll-Like Receptor 4/*genetics
MH  - Trans-Activators/*physiology
MH  - *Transcription Initiation Site
EDAT- 2007/07/12 09:00
MHDA- 2007/10/20 09:00
CRDT- 2007/07/12 09:00
PHST- 2007/07/12 09:00 [pubmed]
PHST- 2007/10/20 09:00 [medline]
PHST- 2007/07/12 09:00 [entrez]
AID - S0021-9258(20)58758-9 [pii]
AID - 10.1074/jbc.M703856200 [doi]
PST - ppublish
SO  - J Biol Chem. 2007 Sep 14;282(37):26874-26883. doi: 10.1074/jbc.M703856200. Epub 
      2007 Jul 10.