Identification and functional analysis of the transcriptional enhancer of the human T cell receptor beta gene.
The productive rearrangement and transcription of T cell receptor (TcR) beta genes is confined to T lymphocytes and is subject to both tissue-specific and developmental regulation. In addition to their function in transcriptional control, cis-acting elements are likely to play a role in the regulation of the rearrangement process. In this report we describe the location of a strong and inducible transcriptional enhancer 3' to the human TcR C beta 2 gene segment. The core enhancer, defined by deletion analysis using a transient transfection assay, resided within 362 bp of DNA. This enhancer core was able to activate transcription from a heterologous promoter and functioned well in T and B lymphocytes, but only minimally in HeLa cells. In contrast, a longer fragment containing the enhancer core showed marked T cell specificity. The enhancer was highly inducible by phorbol esters, the molecular basis for the inducibility residing within a 118-bp region of the enhancer core. This inducibility may be important in modulation of TcR beta gene expression during T cell differentiation and/or activation.
Prosser
H M
HM
Imperial Cancer Research Fund, St. Bartholomew's Hospital, London.
Lake
R A
RA
Wotton
D
D
Owen
M J
MJ
D001483:Base Sequence; D003001:Cloning, Molecular; D004252:DNA Mutational Analysis; D004742:Enhancer Elements, Genetic; D005786:Gene Expression Regulation; D005796:Genes; D006801:Humans; D008221:Lymphoid Tissue / Q000502:physiology; D008969:Molecular Sequence Data; D010703:Phorbol Esters / Q000494:pharmacology; D011948:Receptors, Antigen, T-Cell / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta; D012045:Regulatory Sequences, Nucleic Acid
D010703:Phorbol Esters; D011948:Receptors, Antigen, T-Cell; D016693:Receptors, Antigen, T-Cell, alpha-beta