A thymus-specific member of the HMG protein family regulates the human T cell receptor C alpha enhancer.
The human T cell-specific transcription factor TCF-1 alpha plays a key role in the tissue-specific activation of the T cell receptor (TCR) C alpha enhancer and binds to pyrimidine-rich elements (5'-PyCTTTG-3') present in a variety of other T cell-specific control regions. Using amino acid sequence information derived from the DNA affinity-purified protein, we have now isolated cDNA clones encoding TCF-1 alpha. The TCF-1 alpha cDNA contains a single 68-amino-acid domain that is homologous to a region conserved among high-mobility group (HMG) and nonhistone chromosomal proteins. Expression of full-length and mutant cDNA clones in bacteria reveal that the single HMG motif, which is predicted to contain two extended alpha-helical segments, is sufficient to direct the sequence-specific binding of TCF-1 alpha to DNA. Northern blot experiments demonstrate further that TCF-1 alpha mRNA is highly tissue specific, found primarily in the thymus or T cell lines. The immature CEM T cell line expresses relatively low levels of TCF-1 alpha mRNA, which are increased upon activation of these cells by phorbol esters. Interestingly, the cloned TCF-1 alpha protein is a potent transcriptional activator of the human TCR alpha enhancer in nonlymphoid cell lines, whereas the activity of the endogenous protein in T cell lines is strongly dependent on an additional T cell-specific protein that interacts with the core enhancer. TCF-1 alpha is currently unique among the newly emerging family of DNA-binding regulatory proteins that share the HMG motif in that it is a highly tissue-specific RNA polymerase II transcription factor.
Waterman
M L
ML
Molecular Biology and Virology Laboratory, Salk Institute, La Jolla, California 92037.
Fischer
W H
WH
Jones
K A
KA
D000595:Amino Acid Sequence; D001483:Base Sequence; D004742:Enhancer Elements, Genetic; D006609:High Mobility Group Proteins / Q000235:genetics*; D006801:Humans; D008969:Molecular Sequence Data; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D012689:Sequence Homology, Nucleic Acid; D013601:T-Lymphocytes / Q000276:immunology*; D013950:Thymus Gland / Q000276:immunology; D014157:Transcription Factors / Q000235:genetics* / Q000302:isolation & purification / Q000378:metabolism
D006609:High Mobility Group Proteins; D015345:Oligonucleotide Probes; D011948:Receptors, Antigen, T-Cell; D014157:Transcription Factors