A new Groucho TLE4 protein may regulate the repressive activity of Pax5 in human B lymphocytes.
During mouse B-cell development, Pax5 is an essential transcription factor that acts as an activator of B-cell-specific genes and as a repressor of alternative lineage fates. The repressive function is mediated by the recruitment of members of the Groucho co-repressor family. Using an RNA display approach, we have isolated a transcript, called QD, specifically expressed in human pro-B and pre-B cells, which is derived from the human Groucho TLE4 gene. The QD transcript contains the first four TLE4 exons and an intronic sequence 3' of exon 4, demonstrating that QD is a splice variant of TLE4. The putative resulting protein of 94 amino acids corresponds to approximately half of an N-terminal tetramerization domain. We also show specific expression of TLE4 transcripts in human B cells and of TLE4 proteins in B-cell nuclei. Moreover, we demonstrate that recombinant QD protein binds to the TLE4 Q domain and is able to abolish the TLE4/Pax5 interaction. Thus, QD could act as a negative regulator of TLE4 function, in early B-cell differentiation.
Milili
Michèle
M
Centre d'Immunologie de Marseille-Luminy, CNRS-INSERM-Univ.Med., Campus de Luminy, Marseille, France.
Gauthier
Laurent
L
Veran
Julie
J
Mattei
Marie-Geneviève
MG
Schiff
Claudine
C
D000595:Amino Acid Sequence; D001402:B-Lymphocytes / Q000166:cytology* / Q000378:metabolism; D001483:Base Sequence; D002460:Cell Line; D046508:Culture Techniques; D018076:DNA, Complementary / Q000235:genetics; D004268:DNA-Binding Proteins / Q000502:physiology*; D006801:Humans; D008969:Molecular Sequence Data; D009687:Nuclear Proteins / Q000502:physiology*; D051757:PAX5 Transcription Factor; D016133:Polymerase Chain Reaction / Q000379:methods; D012097:Repressor Proteins / Q000502:physiology*; D014157:Transcription Factors / Q000502:physiology*
D018076:DNA, Complementary; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; D051757:PAX5 Transcription Factor; C497281:PAX5 protein, human; D012097:Repressor Proteins; C465817:TLE4 protein, human; D014157:Transcription Factors