The T-cell receptor (TCR) -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  gene uncovers a surprisingly complex and tissue-specific structure at the TCR V 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.T-cell-specific expression of the T-cell receptor (TCR)-CD3 complex and the CD4-CD8 coreceptors depends on distal enhancer elements (8,18,22,29,31,38,46,64,78,80), which is reminiscent of the B-cell-specific regulation of transcription of the immunoglobulin genes (4). The enhancers contain multiple binding sites for ubiquitous, lymphoid cell-and T-cell-specific factors (reviewed in references 9 and 40). Many T-cell-and lymphoid cell-specific factors were initially identified because they bind to functional important elements of the TCR enhancers. Examples are members of the family of high-mobilitygroup (HMG) box-containing factors TCF1 and LEF1 (T-cell factor 1 and lymphoid enhancer binding factor 1) (74,75,77), the zinc finger protein Ikaros (17,49), and the runt domain factor PEBP2␣ (polyomavirus enhancer binding protein 2␣). The latter, also called CBF␣ (core binding factor ␣), is the murine homolog of human AML1 (52), which is involved in the induction of acute myeloid leukemia (reviewed in references 30 and 50). In addition, the lymphoid cell-specific factors Ets-1, Elf-1, and GATA3 as well as the ubiquitous CREB/ATF family bind to and activate the TCR enhancers (16,20,28,43,79,80).Expression of the TCR genes is dependent on distal enhancers (22,38,40,46). Like other tissue-specific and inducible enhancer elements (for reviews, see references 72 and 73), the TCR enhancers assemble the transcription factors in a complex multiprotein structure (19,20). The corresponding promoters are thought to contribute little to tissue-specific transcription of TCR genes (40). For example, sequence comparisons of the different -chain promoters revealed only one conserved element (1, 59, 69). It resembles a cyclic AMPresponsive element (CRE) and is recognized by different members o...
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.