Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.

Previously, we reported the isolation of cDNA clones representing four alternative splice forms of TCF-1, a T-cell-specific transcription factor. In the present study, Western blotting (immunoblotting) yielded a multitude of TCF-1 proteins ranging from 25-55 kDa, a pattern not simply explained from...

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Main Authors: Van de Wetering, M, Castrop, J, Korinek, V, Clevers, H
Formato: Artigo
Idioma:en
Publicado em: 1996
Assuntos:
Research Article
Acesso em linha:https://ncbi.nlm.nih.gov/pmc/articles/PMC231054/
https://ncbi.nlm.nih.gov/pubmed/8622675
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spelling pubmed-2310542003-10-28 Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties. Van de Wetering, M Castrop, J Korinek, V Clevers, H Mol Cell Biol Research Article Previously, we reported the isolation of cDNA clones representing four alternative splice forms of TCF-1, a T-cell-specific transcription factor. In the present study, Western blotting (immunoblotting) yielded a multitude of TCF-1 proteins ranging from 25-55 kDa, a pattern not simply explained from the known splice alternatives. Subsequent cDNA cloning, PCR amplification, and analysis by rapid amplification of 5' cDNA ends revealed (i) the presence of an alternative upstream promoter, which extended the known N terminus by 116 amino acids, (ii) the presence of four alternative exons, and (iii) the existence of a second reading frame in the last exon encoding an extended C terminus. Inclusion of the extended N terminus into the originally reported protein resulted in a striking similarity to the lymphoid factor Lef-1. Several of the TCF-1 isoforms, although less potent, mimicked Lef-1 in transactivating transcription through the T-cell receptor alpha-chain (TCR-alpha) enhancer. These data provide a molecular basis for the complexity of the expressed TCF-1 proteins and establish the existence of functional differences between these isoforms. Furthermore, the functional redundancy between Tcf-1 and Lef-1 explains the apparently normal TCR-alpha expression in single Tcf-1 or Lef-1 knockout mice despite the firm in vitro evidence for the importance of the Tcf/Lef site in the TCR-alpha enhancer. 1996-03 /pmc/articles/PMC231054/ /pubmed/8622675 Text en
institution US National Library of Medicine
collection PubMed Central
language en
format Article
topic Research Article
spellingShingle Research Article
Van de Wetering, M
Castrop, J
Korinek, V
Clevers, H
Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
description Previously, we reported the isolation of cDNA clones representing four alternative splice forms of TCF-1, a T-cell-specific transcription factor. In the present study, Western blotting (immunoblotting) yielded a multitude of TCF-1 proteins ranging from 25-55 kDa, a pattern not simply explained from the known splice alternatives. Subsequent cDNA cloning, PCR amplification, and analysis by rapid amplification of 5' cDNA ends revealed (i) the presence of an alternative upstream promoter, which extended the known N terminus by 116 amino acids, (ii) the presence of four alternative exons, and (iii) the existence of a second reading frame in the last exon encoding an extended C terminus. Inclusion of the extended N terminus into the originally reported protein resulted in a striking similarity to the lymphoid factor Lef-1. Several of the TCF-1 isoforms, although less potent, mimicked Lef-1 in transactivating transcription through the T-cell receptor alpha-chain (TCR-alpha) enhancer. These data provide a molecular basis for the complexity of the expressed TCF-1 proteins and establish the existence of functional differences between these isoforms. Furthermore, the functional redundancy between Tcf-1 and Lef-1 explains the apparently normal TCR-alpha expression in single Tcf-1 or Lef-1 knockout mice despite the firm in vitro evidence for the importance of the Tcf/Lef site in the TCR-alpha enhancer.
author Van de Wetering, M
Castrop, J
Korinek, V
Clevers, H
author_facet Van de Wetering, M
Castrop, J
Korinek, V
Clevers, H
author_sort Van de Wetering, M
title Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
title_short Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
title_full Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
title_fullStr Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
title_full_unstemmed Extensive alternative splicing and dual promoter usage generate Tcf-1 protein isoforms with differential transcription control properties.
title_sort extensive alternative splicing and dual promoter usage generate tcf-1 protein isoforms with differential transcription control properties.
publishDate 1996
url https://ncbi.nlm.nih.gov/pmc/articles/PMC231054/
https://ncbi.nlm.nih.gov/pubmed/8622675
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