Document Detail


PEBP2 and c-myb sites crucial for lambda5 core enhancer activity in pre-B cells.
MedLine Citation:
PMID:  11745333     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The lambda5 gene is expressed exclusively in precursor (pre-) B cells where its gene product, as part of the pre-B cell receptor, is crucial for the proliferation of these cells. Several DNA regions regulate the activity and expression pattern of the lambda5 gene. Amongst these is an enhancer, B(lambda5), located 5' of the gene. Here we analyze the lambda5 enhancer core, b(lambda5), which in earlier experiments was demonstrated to retain 50% of the enhancer activity, and show that this activity is restricted to pre-B cells. We identify a DNA element within b(lambda5), PEBP2(lambda5), which is essential for enhancer activity: mutation within this site dramatically reduces core enhancer activity in pre-B cells. The PEBP2(lambda5) site binds bacterially produced polyoma enhancer binding proteins (PEBP) (Runx/AML/CBFA). Furthermore, PEBP2 proteins present in nuclear extracts from murine pre-B cells bind to the PEBP2(lambda5) element. PEBP2 proteins in mature B cells also bind to the PEBP2(lambda5 )element, implying that if PEBP2 proteins are responsible for the stage-specific expression, they have to be non-activating or inhibiting in mature B cells. We also demonstrate that a described partner of PEBP2, c-myb, binds to a sequence termed myb(lambda5) located just upstream of the PEBP2(lambda5) site in the core enhancer. The myb(lambda5) element is also crucial for enhancer activity, since mutating the myb site reduces core enhancer activity to the same extent as mutating the PEBP2 site. Earlier reports have shown that c-myb is expressed at high levels in pre-B cell lines whereas its expression is down-regulated in more mature B cell lines. Thus, c-myb may be involved in determining the stage-specific expression of the lambda5 gene.
Authors:
A Mårtensson; X Q Xie; C Persson; M Holm; T Grundström; I L Mårtensson
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  European journal of immunology     Volume:  31     ISSN:  0014-2980     ISO Abbreviation:  Eur. J. Immunol.     Publication Date:  2001 Nov 
Date Detail:
Created Date:  2001-12-17     Completed Date:  2002-01-03     Revised Date:  2008-11-21    
Medline Journal Info:
Nlm Unique ID:  1273201     Medline TA:  Eur J Immunol     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  3165-74     Citation Subset:  IM    
Affiliation:
Department of Cell- and Molecular Biology, Lund University, Lund, Sweden.
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MeSH Terms
Descriptor/Qualifier:
Animals
B-Lymphocytes / metabolism*
Binding Sites
Core Binding Factor beta Subunit
DNA-Binding Proteins / physiology*
Enhancer Elements, Genetic / physiology*
Hematopoietic Stem Cells / metabolism*
Immunoglobulin lambda-Chains / genetics*
Mice
Proto-Oncogene Proteins c-myb / physiology*
Transcription Factor AP-2
Transcription Factors / physiology*
Chemical
Reg. No./Substance:
0/Cbfb protein, mouse; 0/Core Binding Factor beta Subunit; 0/DNA-Binding Proteins; 0/Immunoglobulin lambda-Chains; 0/Proto-Oncogene Proteins c-myb; 0/Transcription Factor AP-2; 0/Transcription Factors

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