A conserved tissue-specific structure at a human T-cell receptor beta-chain core promoter.
The T-cell receptor (TCR) beta-chain promoters have been characterized as nonstructured basal promoters that carry a single conserved ubiquitous cyclic AMP-responsive element. Our investigation of the human TCR beta gene uncovers a surprisingly complex and tissue-specific structure at the TCR Vbeta 8.1 promoter. The core of the promoter (positions -42 to +11) is recognized by the lymphoid cell-specific transcription factors Ets-1, LEF1, and AML1 as well as by CREB/ATF-1, as is demonstrated in gel shift and footprinting experiments. With the exception of LEF1, these factors activate transcription in T cells. Binding sites at the core region show little conservation with consensus sites. Nonetheless, CREB, Ets-1, and AML1 bind and activate cooperatively and very efficiently through the nonconsensus binding sites at the core promoter region. Moderate ubiquitous activation is further induced by CREB/ATF and Sp1 factors through proximal upstream elements. The tissue-specific core promoter structure is apparently conserved in other T-cell-specifically expressed genes such as the CD4 gene. Our observations suggest that both the enhancer and the promoter have a complex tissue-specific structure whose functional interplay potentiates T-cell-specific transcription.
Halle
J P
JP
Laboratorium für Molekulare Biologie-Genzentrum der Ludwig-Maximilians-Universität München, Munich, Germany.
Haus-Seuffert
P
P
Woltering
C
C
Stelzer
G
G
Meisterernst
M
M
D001483:Base Sequence; D001665:Binding Sites; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D016384:Consensus Sequence / Q000235:genetics; D017124:Conserved Sequence / Q000235:genetics*; D004247:DNA / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D019169:Jurkat Cells; D008969:Molecular Sequence Data; D009154:Mutation; D009928:Organ Specificity; D011401:Promoter Regions, Genetic / Q000235:genetics*; D016693:Receptors, Antigen, T-Cell, alpha-beta / Q000235:genetics*; D014157:Transcription Factors / Q000378:metabolism; D015533:Transcriptional Activation / Q000235:genetics
D016693:Receptors, Antigen, T-Cell, alpha-beta; D014157:Transcription Factors; D004247:DNA