PMID- 10510379
OWN - NLM
STAT- MEDLINE
DCOM- 19991104
LR  - 20081121
IS  - 0022-1767 (Print)
IS  - 0022-1767 (Linking)
VI  - 163
IP  - 8
DP  - 1999 Oct 15
TI  - Functional synergism of STAT6 with either NF-kappa B or PU.1 to mediate
      IL-4-induced activation of IgE germline gene transcription.
PG  - 4383-91
AB  - Ig heavy chain class switching to IgE is directed by IL-4 and IL-13 by inducing
      transcription from the IgE germline promoter. A crucial transcription factor in
      this process is STAT6, which binds to a specific DNA element upon cytokine
      activation. In this paper it is shown that the B cell- and monocyte-specific
      factor PU.1 interacts with a closely spaced sequence in the human IgE germline
      promoter that overlaps with a previously described binding site for NF kappa
      B/rel. The authenticity of PU.1 was demonstrated by specific competition and
      supershifts in EMSA experiments. In addition, in vitro translated PU.1 could
      interact with an oligonucleotide derived from the IgE germline promoter
      containing the PU.1 binding site and migrated with the same mobility compared
      with the complex formed with nuclear extracts. Transient transfection experiments
      using IgE germline promoter reporter gene constructs demonstrated that mutations 
      affecting DNA binding of PU.1 or NF kappa B/rel had no or little effect on IL-4
      inducibility of these plasmids. However, point mutations that abolished binding
      of both factors abrogated cytokine inducibility. No strict spacing of the STAT6
      and the composite PU. 1/NF-kappa B elements is required for IL-4 induction.
      IL-4-induced STAT6 DNA binding was retained in PU.1-/NF kappa B/rel- double
      mutants. The data demonstrate that cooperation of STAT6 with at least PU.1 or NF 
      kappa B/rel is necessary for IL-4-induced activation of IgE germline gene
      transcription.
FAU - Stutz, A M
AU  - Stutz AM
AD  - Department of Immunology, Novartis Research Institute, Vienna, Austria.
FAU - Woisetschlager, M
AU  - Woisetschlager M
LA  - eng
PT  - Journal Article
PL  - United States
TA  - J Immunol
JT  - Journal of immunology (Baltimore, Md. : 1950)
JID - 2985117R
RN  - 0 (Adjuvants, Immunologic)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (NF-kappa B)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (STAT6 protein, human)
RN  - 0 (Trans-Activators)
RN  - 0 (Transcription Factors)
RN  - 0 (proto-oncogene protein Spi-1)
RN  - 207137-56-2 (Interleukin-4)
RN  - 37341-29-0 (Immunoglobulin E)
SB  - AIM
SB  - IM
MH  - Adjuvants, Immunologic/metabolism/*physiology
MH  - Base Sequence
MH  - DNA-Binding Proteins/physiology
MH  - Drug Synergism
MH  - Gene Expression Regulation/*immunology
MH  - Humans
MH  - Immunoglobulin E/*genetics/metabolism
MH  - Interleukin-4/biosynthesis/genetics/*physiology
MH  - Molecular Sequence Data
MH  - NF-kappa B/metabolism/*physiology
MH  - Promoter Regions, Genetic/immunology
MH  - Protein Binding/genetics/immunology
MH  - Proto-Oncogene Proteins/genetics/metabolism/*physiology
MH  - Proto-Oncogene Proteins c-ets
MH  - STAT6 Transcription Factor
MH  - Trans-Activators/genetics/metabolism/*physiology
MH  - Transcription Factors/genetics/metabolism
MH  - Transcription, Genetic/*immunology
MH  - Tumor Cells, Cultured
EDAT- 1999/10/08 00:00
MHDA- 1999/10/08 00:01
CRDT- 1999/10/08 00:00
PHST- 1999/10/08 00:00 [pubmed]
PHST- 1999/10/08 00:01 [medline]
PHST- 1999/10/08 00:00 [entrez]
AID - ji_v163n8p4383 [pii]
PST - ppublish
SO  - J Immunol. 1999 Oct 15;163(8):4383-91.