PMID- 8466864
OWN - NLM
STAT- MEDLINE
DCOM- 19930507
LR  - 20190512
IS  - 0953-8178 (Print)
IS  - 0953-8178 (Linking)
VI  - 5
IP  - 3
DP  - 1993 Mar
TI  - The human I alpha 1 and I alpha 2 germline promoter elements: proximal positive 
      and distal negative elements may regulate the tissue specific expression of C 
      alpha 1 and C alpha 2 germline transcripts.
PG  - 271-82
AB  - Treatment of human splenic B lymphocytes with the mitogen Branhamella catarrhalis 
      (BC) and transforming growth factor-beta 1 (TGF-beta 1) induces expression of 
      germline Ig C alpha transcripts and class switching to this isotype. To further 
      characterize the molecular mechanism by which TGF-beta 1 and mitogenic signals 
      regulate the expression of unrearranged C alpha 1 and C alpha 2 genes, we have 
      characterized the promoter elements that are responsible for the transcriptional 
      activation of their corresponding germline genes using transient expression 
      assays. We report here that both in the I alpha 1 and the I alpha 2 regions, 
      maximal phorbol myristate acetate (PMA) and TGF-beta 1 responsiveness of the 
      promoters can be conferred by 327 bp spanning the transcription initiation sites 
      and a previously identified phylogenetically conserved region. The expression of 
      these 327 bp segments is not restricted to the B cell lineage since they are also 
      active in the erythroleukemia cell line K562 as well as the B cell lines Raji and 
      DG75. Mutational analyses have demonstrated the importance of sequences within 
      the 327 bp segment that contain a putative cyclic AMP responsive element binding 
      protein (CREB) binding site for TGF-beta 1 and PMA responsiveness and putative 
      PU-1 and Sp1 binding sites for basal promoter activity. Upstream distal elements 
      that could negatively modulate the expression of the I alpha 1 and I alpha 2 
      promoters, particularly in non-B cells, have been identified. Three such elements 
      were mapped between positions -352 to -243, -627 to -516, and upstream of 
      position -731 respectively. The influence of these elements presumably 
      contributes to the B cell specific expression of the I alpha 1 and I alpha 2 
      promoters. The I alpha 1 and I alpha 2 promoters were found to be functionally 
      indistinguishable from each other with respect to their basal level of 
      expression, and their responsiveness to TGF-beta 1.
FAU - Lars, N
AU  - Lars N
AD  - Department for Cell and Molecular Biology, Umea University, Sweden.
FAU - Paschalis, S
AU  - Paschalis S
LA  - eng
SI  - GENBANK/L04540
SI  - GENBANK/L04541
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Int Immunol
JT  - International immunology
JID - 8916182
RN  - 0 (Immunoglobulin Constant Regions)
RN  - 0 (Immunoglobulin Isotypes)
RN  - 0 (Transforming Growth Factor beta)
RN  - 9007-49-2 (DNA)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - B-Lymphocytes/immunology
MH  - Base Sequence
MH  - Cell Line
MH  - Chromosome Mapping
MH  - DNA/genetics
MH  - Gene Expression Regulation/drug effects
MH  - *Genes, Immunoglobulin
MH  - Humans
MH  - Immunoglobulin Constant Regions/*genetics
MH  - Immunoglobulin Isotypes/genetics
MH  - Molecular Sequence Data
MH  - Mutation
MH  - *Promoter Regions, Genetic
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transforming Growth Factor beta/pharmacology
EDAT- 1993/03/01 00:00
MHDA- 1993/03/01 00:01
CRDT- 1993/03/01 00:00
PHST- 1993/03/01 00:00 [pubmed]
PHST- 1993/03/01 00:01 [medline]
PHST- 1993/03/01 00:00 [entrez]
AID - 10.1093/intimm/5.3.271 [doi]
PST - ppublish
SO  - Int Immunol. 1993 Mar;5(3):271-82. doi: 10.1093/intimm/5.3.271.