A conserved sequence in the T-cell receptor beta-chain promoter region.

Anderson, Steven J.; Chou, Hubert S.; Loh, Dennis Y.

doi:10.1073/pnas.85.10.3551

Cited by 70 publications

(40 citation statements)

References 40 publications

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“…Northern blots containing SL12.4 poly(A)+ RNA were hybridized with a C,31-specific probe. Figure 1B shows that there was no evidence for mature 1.3- were derived either from published work (1,8,14) or from our sequence analysis of the expressed V35.1 element in SL12.4 cells.…”

mentioning

confidence: 77%

T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates.

Qian¹,

Theodor²,

Carter³

et al. 1993

Mol. Cell. Biol.

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The expression of functional T cell receptor-n (TCR-13) transcripts requires the activation of programmed DNA rearrangement events. It is not clear whether other mechanisms dictate TCR-1 mRNA levels during thymic ontogeny. We examined the potential role of RNA splicing as a regulatory mechanism. As a model system, we used an immature T cell clone, SL12.4, that transcribes a fully rearranged TCR-13 gene but essentially lacks mature 1.3-kb TCR-1 transcripts in the cytoplasm. Abundant TCR-13 splicing intermediates accumulate in the nucleus of this cell clone. These splicing intermediates result from inefficient or inhibited excision of four of the five TCR-13 introns; the only intron that is efficiently spliced is the most 5' intron, IVSL.The focal point for the regulation appears to be IVSlc31 and IVS2cp1, since unusual splicing intermediates that have cleaved the 5' splice site but not the 3' splice site of these two introns accumulate in vivo. The block in 3' splice site cleavage is of interest since sequence analysis reveals that these two introns possess canonical splice sites. A repressional mechanism involving a labile repressor protein may be responsible for the inhibition of RNA splicing since treatment of SL12.4 cells with the protein synthesis inhibitor cycloheximide reversibly induces a rapid and dramatic accumulation of fully spliced TCR-13 transcripts in the cytoplasm, concomitant with a decline in TCR-13 pre-mRNAs in the nucleus. This inducible system may be useful for future studies analyzing the underlying molecular mechanisms that regulate RNA splicing.The T cell receptor (TCR) for antigen is a multisubunit receptor composed of two variable chains that recognize antigen (either the TCR-ot and -I or and several CD3 invariant chains that are involved in signal transduction (2). TCR-13 chains are of particular interest for several reasons, including the fact that they recognize socalled superantigens found in the natural environment (18 The expression of TCR-P transcripts during T cell maturation has been well studied. Truncated (1.0-kb) TCR-0 transcripts are expressed very early in murine ontogeny (at least as early as day 14 of mouse gestation) along with CD3--y, -8, -£, and -t transcripts (11,16,42 thymocytes undergo rearrangement events in the thymus, but it also may be due to alterations in transcriptional or posttranscriptional regulatory events. On day 17, TCR-ot transcripts become apparent in the fetal thymus (11,42). This event roughly coincides with the appearance of cell surface TCR-ot3 protein on a small proportion of fetal thymocytes (42). Thus, the TCR-ao chain appears to be the limiting subunit that controls the surface expression of TCR-aIt protein early in ontogeny. TCR-P protein has also been detected on the surface of immature thymocytes or cell lines in the absence of the TCR-oL chain (21, 33), but its function in this context is not yet known.The transcriptional regulation of the TCR-13 gene has been studied in cell culture. A tissue-specific enhancer element has been defined 3'...

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confidence: 77%

T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates.

Qian¹,

Theodor²,

Carter³

et al. 1993

Mol. Cell. Biol.

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“…The CRE is highly conserved, and also Sp1 recognition sites have been described in the context of others such as the TCR V␣ promoter (37). CREB/ATF factors bind to the upstream CRE that is conserved between most TCR V␤ promoters (1,2,16,39,59). Surprisingly, CREB and also ATF-1 activate transcription efficiently through the core region but barely affect promoter activity through the conserved upstream CRE.…”

Section: Discussionmentioning

confidence: 99%

“…Mutational analysis of a murine TCR V␤ promoter suggested that the CRE is the only promoter element that is required for transcriptional activation (2). With the exception of the CRE, TCR promoters seemed to be unrelated, based on previous reports (1,59,69). On certain individual promoters, functional binding of ubiquitous transcription factors such as Sp1 (37) and TFII-I (42) could be demonstrated.…”

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confidence: 98%

“…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 of the ubiquitous CREB/ATF family of transcription factors (2,16,39).…”

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confidence: 99%

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A Conserved Tissue-Specific Structure at a Human T-Cell Receptor β-Chain Core Promoter

Halle

Haus-Seuffert

Woltering

et al. 1997

Molecular and Cellular Biology

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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...

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“…1). Within this region, we assayed the conserved decamer sequence (45,46) in several V␤ promoters (V␤12P, V␤11P, V␤9P), the RSS elements flanking V␤ segments (V␤13R, V␤12R, V␤11R, V␤9R, V␤6R), and several intergenic sites located between V␤ segments. To assay D␤J␤ chromatin we analyzed a site in PD␤1 (47,48), just upstream of the D␤1 gene segment.…”

Section: Structure Of Tcr ␤ Locus Chromatin In Dn Thymocytesmentioning

confidence: 99%

A Change in the Structure of Vβ Chromatin Associated with TCR β Allelic Exclusion

Tripathi

Jackson

Krangel

2002

The Journal of Immunology

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To investigate chromatin control of TCR β rearrangement and allelic exclusion, we analyzed TCR β chromatin structure in double negative (DN) thymocytes, which are permissive for TCR β recombination, and in double positive (DP) thymocytes, which are postallelic exclusion and nonpermissive for Vβ to DβJβ recombination. Histone acetylation mapping and DNase I sensitivity studies indicate Vβ and DβJβ segments to be hyperacetylated and accessible in DN thymocytes. However, they are separated from each other by hypoacetylated and inaccessible trypsinogen chromatin. The transition from DN to DP is accompanied by selective down-regulation of Vβ acetylation and accessibility. The level of DP acetylation and accessibility is minimal for five of six Vβ segments studied but remains substantial for one. Hence, the observed changes in Vβ chromatin structure appear sufficient to account for allelic exclusion of many Vβ segments. They may contribute to, but not by themselves fully account for, allelic exclusion of others.

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A conserved sequence in the T-cell receptor beta-chain promoter region.

Cited by 70 publications

References 40 publications

T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates.

T cell receptor-beta mRNA splicing: regulation of unusual splicing intermediates.

A Conserved Tissue-Specific Structure at a Human T-Cell Receptor β-Chain Core Promoter

A Change in the Structure of Vβ Chromatin Associated with TCR β Allelic Exclusion

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