LyF-1, a transcriptional regulator that interacts with a novel class of promoters for lymphocyte-specific genes.
We have studied transcriptional control of the murine terminal deoxynucleotidyltransferase (TdT) gene, which is activated specifically in immature B and T lymphocytes. This analysis has led to the identification and purification of a 50-kDa sequence-specific DNA-binding protein, LyF-1, that interacts with the approximate consensus sequence PyPyTGGGAGPu and is enriched in cells at most stages of B- and T-cell differentiation. LyF-1 binds tightly to an element in the TdT promoter that we show is required for transcription in lymphocytes. LyF-1 also interacts with an element in the immunoglobulin mu enhancer, called microB, that was recently shown to be important for lymphocyte-specific enhancer activity. Moreover, LyF-1 binds to the promoters for the lymphocyte-specific genes lambda 5, VpreB, and lck, all of which we speculate have additional features in common with the TdT promoter. Thus, LyF-1 may be a general transcriptional activator for genes whose expression is restricted to the B- and/or T-lymphocyte lineages.
Howard Hughes Medical Institute, Molecular Biology Institute, UCLA School of Medicine 90024.
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D000818:Animals; D001483:Base Sequence; D002454:Cell Differentiation / Q000502:physiology; D002460:Cell Line; D004252:DNA Mutational Analysis; D004254:DNA Nucleotidyltransferases / Q000235:genetics*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004742:Enhancer Elements, Genetic / Q000502:physiology; D015870:Gene Expression / Q000502:physiology; D000882:Haplorhini; D007145:Immunoglobulin kappa-Chains / Q000235:genetics; D007148:Immunoglobulin mu-Chains / Q000235:genetics; D008214:Lymphocytes / Q000201:enzymology / Q000378:metabolism*; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000502:physiology*; D012689:Sequence Homology, Nucleic Acid; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
D004268:DNA-Binding Proteins; D007145:Immunoglobulin kappa-Chains; D007148:Immunoglobulin mu-Chains; D014157:Transcription Factors; D004254:DNA Nucleotidyltransferases