PMID- 10369418
OWN - NLM
STAT- MEDLINE
DCOM- 19990629
LR  - 20081121
IS  - 0161-5890 (Print)
IS  - 0161-5890 (Linking)
VI  - 36
IP  - 1
DP  - 1999 Jan
TI  - Regulation of the germline immunoglobulin Cgamma1 promoter by CD40 ligand and
      IL-4: dual role for tandem NF-kappaB binding sites.
PG  - 31-44
AB  - Transcription of germline Ig constant region genes and associated switch regions 
      is an early and essential step in heavy chain class switch recombination.
      Transcription of the germline Cgamma1 and C epsilon Ig genes is induced by IL-4
      via STAT6 activation; CD40 signaling can independently induce transcription of
      these genes and act in synergy with IL-4 to increase expression. In the present
      study, we investigated the role of three tandem NF-kappaB sites (site 1, -95;
      site 2, -71; site 3, -53) in the regulation of the germline Cgamma1 Ig promoter
      by CD40 Ligand (CD40L) and IL-4 in the mouse B lymphoma cell line, BCL1-3B3.
      Germline gamma1 transcripts are induced by CD40L and by IL-4 in BCL1-3B3 and the 
      combination of signals is synergistic, as in normal B cells. EMSA with crude
      nuclear extracts demonstrated that stimulation with CD40L results in the
      induction of NF-kappaB complexes that bind to each of the three NF-kappaB sites
      and are composed mainly of p50 and RelB, but also include c-Rel and p65.
      Surprisingly, site-specific mutagenesis of the NF-kappaB sites did not reduce
      CD40-responsiveness of germline gamma1 promoter-luciferase reporter constructs
      transiently transfected into BCL1-3B3. Mutation in any one NF-kappaB site,
      however, significantly reduced overall transcriptional activity of the promoter, 
      both basal and induced, suggesting a role in basal promoter function. In
      addition, activation of the promoter by IL-4 was blocked by mutation of all three
      NF-kappaB sites and similarly reduced by mutation of site 1, suggesting that
      NF-kappaB-STAT6 interactions may be necessary for STAT6-mediated transactivation 
      of the germline gamma1 promoter. The results suggest that the three NF-kappaB
      sites may serve as a focus for formation of a higher-order transcription complex 
      including STAT6, NF-kappaB and components of the basal transcription apparatus.
FAU - Warren, W D
AU  - Warren WD
AD  - Department of Microbiology, University of Texas Health Science Center at San
      Antonio, 78284-7758, USA.
FAU - Roberts, K L
AU  - Roberts KL
FAU - Linehan, L A
AU  - Linehan LA
FAU - Berton, M T
AU  - Berton MT
LA  - eng
GR  - AI36310/AI/NIAID NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Mol Immunol
JT  - Molecular immunology
JID - 7905289
RN  - 0 (Immunoglobulin G)
RN  - 0 (Membrane Glycoproteins)
RN  - 0 (NF-kappa B)
RN  - 0 (STAT6 Transcription Factor)
RN  - 0 (Stat6 protein, mouse)
RN  - 0 (Trans-Activators)
RN  - 147205-72-9 (CD40 Ligand)
RN  - 207137-56-2 (Interleukin-4)
SB  - IM
MH  - Animals
MH  - B-Lymphocytes/*immunology
MH  - Base Sequence
MH  - CD40 Ligand
MH  - Female
MH  - Gene Expression Regulation/*drug effects/*immunology
MH  - *Genes, Immunoglobulin
MH  - Immunoglobulin G/*genetics/immunology
MH  - Interleukin-4/immunology/*pharmacology
MH  - Membrane Glycoproteins/immunology/*pharmacology
MH  - Mice
MH  - Mice, Inbred BALB C
MH  - Molecular Sequence Data
MH  - NF-kappa B/*immunology
MH  - Promoter Regions, Genetic/drug effects
MH  - STAT6 Transcription Factor
MH  - Trans-Activators/immunology
EDAT- 1999/06/16 00:00
MHDA- 1999/06/16 00:01
CRDT- 1999/06/16 00:00
PHST- 1999/06/16 00:00 [pubmed]
PHST- 1999/06/16 00:01 [medline]
PHST- 1999/06/16 00:00 [entrez]
AID - S016158909800114X [pii]
PST - ppublish
SO  - Mol Immunol. 1999 Jan;36(1):31-44.