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PMID: 8890174 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

E47 activates the Ig-heavy chain and TdT loci in non-B cells.

The EMBO journal ·Vol. 15 ·No. 18 ·1996-09-16 ·Pages 5014-21

Choi JK, Shen CP, Radomska HS, Eckhardt LA, Kadesch T

Abstract

The E2A proteins, E12 and E47, are basic helix-loop-helix (bHLH) proteins essential for the B-cell lineage. Initially identified as immunoglobulin enhancer-binding proteins, they have also been shown to activate immunoglobulin enhancer-based reporters in transient transfection assays. Here, we examine the relationship between E2A DNA binding activity and activation of the endogenous, chromosomal immunoglobulin heavy chain (IgH) locus. Using sterile I(mu) transcription as an indicator of IgH enhancer activity, we see a direct correlation between E2A DNA binding activity and I(mu) transcription in stable BxT hybrids. We also observe a 1000-fold stimulation of endogenous I(mu) transcription in fibroblasts that express high levels of E47 and less stimulation in cells that express E12. By contrast, none of the other IgH enhancer-binding proteins tested (E2-2, Pu.1, Oct-2, OCA-B, TFE3 and USF) were able to activate I(mu) transcription. E47 overexpression also resulted in transcriptional activation of the endogenous gene encoding TdT, indicating that it, too, is a target of E2A proteins early in the B-cell lineage. Our results indicate that E2A proteins have the distinctive property of activating silent, chromatin-embedded B-cell-specific genes, underscoring their crucial role in B-cell development.

MeSH Terms
3T3 Cells Animals B-Lymphocytes/metabolism Binding Sites DNA/metabolism DNA Nucleotidylexotransferase/genetics,metabolism DNA-Binding Proteins/metabolism Fibroblasts/metabolism Helix-Loop-Helix Motifs Immunoglobulin Heavy Chains/metabolism Mice Plasmids/metabolism Polymerase Chain Reaction T-Lymphocytes/metabolism TCF Transcription Factors Transcription Factor 7-Like 1 Protein Transcription Factors/metabolism Transcription, Genetic
Chemicals
DNA-Binding Proteins Immunoglobulin Heavy Chains TCF Transcription Factors Tcf7l1 protein, mouse Transcription Factor 7-Like 1 Protein Transcription Factors DNA DNA Nucleotidylexotransferase
Authors & Affiliations
5 authors, click to expand affiliations / ORCID
Choi J K
Department of Genetics and Pathology, University of Pennsylvania School of Medicine, Philadelphia 19104-6145, USA.
Shen C P
Radomska H S
Eckhardt L A
Kadesch T
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Article Info
Journal
The EMBO journal
Abbr.
EMBO J
ISSN
0261-4189
Published
1996-09-16
Pages
5014-21
Language
English
Region
England
NLM ID
8208664
PMCID
PMC452239
Subset
IM
External Links
PubMed source PMC Full Text View journal details
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