A novel POU domain protein which binds to the T-cell receptor beta enhancer

1993 ◽  
Vol 13 (9) ◽  
pp. 5450-5460
Author(s):  
H Messier ◽  
H Brickner ◽  
J Gaikwad ◽  
A Fotedar
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Function ◽  
Cell Receptor ◽  
Pou Domain ◽  
Specific Manner ◽  
T Cell Receptor Beta ◽  
Domain Protein ◽  
Beta Enhancer

POU domain proteins have been implicated in the regulation of a number of lineage-specific genes. Among the first POU domain proteins described were the immunoglobulin octamer-binding proteins Oct-1 and Oct-2. It was therefore of special interest when we identified a novel lymphoid POU domain protein in Southwestern (DNA-protein) screens of T-cell lambda gt11 libraries. This novel POU protein, TCF beta 1, binds in a sequence-specific manner to a critical motif in the T-cell receptor (TCR) beta enhancer. Sequence analysis revealed that TCF beta 1 represents a new class of POU domain proteins which are distantly related to other POU proteins. TCF beta 1 is encoded by multiple exons whose organization is distinct from that of other POU domain proteins. The expression of TCF beta 1 in a tissue-restricted manner and its ability to bind to multiple motifs in the TCR beta enhancer support a role in regulating TCR beta gene expression. The expression of TCF beta 1 in both B and T cells and the ability of recombinant TCF beta 1 to bind octamer and octamer-related motifs suggest that TCF beta 1 has additional roles in lymphoid cell function. The ability of TCF beta 1 to transactivate in a sequence-specific manner is consistent with a role for regulating lymphoid gene expression.

scholarly journals A novel POU domain protein which binds to the T-cell receptor beta enhancer.

1993 ◽  
Vol 13 (9) ◽  
pp. 5450-5460 ◽  
Author(s):  
H Messier ◽  
H Brickner ◽  
J Gaikwad ◽  
A Fotedar
Keyword(s):  
Gene Expression ◽  
T Cell ◽  
T Cell Receptor ◽  
Cell Function ◽  
Cell Receptor ◽  
Pou Domain ◽  
Specific Manner ◽  
T Cell Receptor Beta ◽  
Domain Protein ◽  
Beta Enhancer

POU domain proteins have been implicated in the regulation of a number of lineage-specific genes. Among the first POU domain proteins described were the immunoglobulin octamer-binding proteins Oct-1 and Oct-2. It was therefore of special interest when we identified a novel lymphoid POU domain protein in Southwestern (DNA-protein) screens of T-cell lambda gt11 libraries. This novel POU protein, TCF beta 1, binds in a sequence-specific manner to a critical motif in the T-cell receptor (TCR) beta enhancer. Sequence analysis revealed that TCF beta 1 represents a new class of POU domain proteins which are distantly related to other POU proteins. TCF beta 1 is encoded by multiple exons whose organization is distinct from that of other POU domain proteins. The expression of TCF beta 1 in a tissue-restricted manner and its ability to bind to multiple motifs in the TCR beta enhancer support a role in regulating TCR beta gene expression. The expression of TCF beta 1 in both B and T cells and the ability of recombinant TCF beta 1 to bind octamer and octamer-related motifs suggest that TCF beta 1 has additional roles in lymphoid cell function. The ability of TCF beta 1 to transactivate in a sequence-specific manner is consistent with a role for regulating lymphoid gene expression.

scholarly journals The t(12;21) translocation converts AML-1B from an activator to a repressor of transcription.

1996 ◽  
Vol 16 (4) ◽  
pp. 1349-1355 ◽  
Author(s):  
S W Hiebert ◽  
W Sun ◽  
J N Davis ◽  
T Golub ◽  
S Shurtleff ◽  
...  
Keyword(s):  
T Cell ◽  
Fusion Protein ◽  
B Cell ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Related Factor ◽  
Core Motif ◽  
T Cell Receptor Beta ◽  
Beta Enhancer ◽  
Receptor Beta

The t(12;21) translocation is present in up to 30% of childhood B-cell acute lymphoblastic and fuses a potential dimerization motif from the ets-related factor TEL to the N terminus of AML1. The t(12;21) translocation encodes a 93-kDa fusion protein that localizes to a high-salt- and detergent-resistant nuclear compartment. This protein binds the enhancer core motif, TGTGGT, and interacts with the AML-1-binding protein, core-binding factor beta. Although TEL/AML-1B retains the C-terminal domain of AML-1B that is required for transactivation of the T-cell receptor beta enhancer, it fails to activate transcription but rather inhibits the basal activity of this enhancer. TEL/AML-1B efficiently interferes with AML-1B dependent transactivation of the T-cell receptor beta enhancer, and coexpression of wild-type TEL does not reverse this inhibition. The N-terminal TEL helix-loop-helix domain is essential for TEL/AML-1B-mediated repression. Thus, the t(12;21) fusion protein dominantly interferes with AML-1B-dependent transcription, suggesting that the inhibition of expression of AML-1 genes is critical for B-cell leukemogenesis.

scholarly journals Development of T3/T cell receptor gene expression in human pre-T neoplasms

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1062-1067
Author(s):  
S Pittaluga ◽  
M Uppenkamp ◽  
J Cossman
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Function ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Surface Expression ◽  
Receptor Repertoire ◽  
Genes Encoding ◽  
T Cell Receptor Beta ◽  
Gene Transcripts

Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.

GATA elements are necessary for the activity and tissue specificity of the T-cell receptor beta-chain transcriptional enhancer

1994 ◽  
Vol 14 (6) ◽  
pp. 4286-4294
Author(s):  
A J Henderson ◽  
S McDougall ◽  
J Leiden ◽  
K L Calame
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Beta Chain ◽  
Transcriptional Enhancer ◽  
T Cell Receptor Beta ◽  
Beta Enhancer ◽  
Receptor Beta

Three high-affinity binding sites for the GATA family of transcriptional regulators have been identified within the T-cell receptor beta-chain (TCR beta) transcriptional enhancer, and their functional significance has been determined in an effort to understand the T-cell specificity of the enhancer more fully. One site, TE4, is important for activity of the enhancer in T cells. Neither site TE1 nor site TE2 can functionally replace a mutated TE4 site in T cells; however, the same protein, probably GATA-3, binds all three sites, as judged by electrophoretic mobility shift, oligonucleotide competition, and proteolytic clipping assays. These data suggest that additional proteins are critical for the ability of GATA-3 to activate the TCR beta enhancer. In fibroblasts, the GATA sequence at site TE1 appears to bind a negative regulator. Since this is not true in B cells, B cells and fibroblasts appear to have different mechanisms for negative regulation of the TCR beta enhancer.

scholarly journals GATA elements are necessary for the activity and tissue specificity of the T-cell receptor beta-chain transcriptional enhancer.

1994 ◽  
Vol 14 (6) ◽  
pp. 4286-4294 ◽  
Author(s):  
A J Henderson ◽  
S McDougall ◽  
J Leiden ◽  
K L Calame
Keyword(s):  
T Cells ◽  
T Cell ◽  
B Cells ◽  
T Cell Receptor ◽  
Cell Receptor ◽  
Beta Chain ◽  
Transcriptional Enhancer ◽  
T Cell Receptor Beta ◽  
Beta Enhancer ◽  
Receptor Beta

Three high-affinity binding sites for the GATA family of transcriptional regulators have been identified within the T-cell receptor beta-chain (TCR beta) transcriptional enhancer, and their functional significance has been determined in an effort to understand the T-cell specificity of the enhancer more fully. One site, TE4, is important for activity of the enhancer in T cells. Neither site TE1 nor site TE2 can functionally replace a mutated TE4 site in T cells; however, the same protein, probably GATA-3, binds all three sites, as judged by electrophoretic mobility shift, oligonucleotide competition, and proteolytic clipping assays. These data suggest that additional proteins are critical for the ability of GATA-3 to activate the TCR beta enhancer. In fibroblasts, the GATA sequence at site TE1 appears to bind a negative regulator. Since this is not true in B cells, B cells and fibroblasts appear to have different mechanisms for negative regulation of the TCR beta enhancer.

Development of T3/T cell receptor gene expression in human pre-T neoplasms

Blood ◽  
1987 ◽  
Vol 69 (4) ◽  
pp. 1062-1067 ◽  
Author(s):  
S Pittaluga ◽  
M Uppenkamp ◽  
J Cossman
Keyword(s):  
T Cell ◽  
T Cell Receptor ◽  
Cell Function ◽  
Receptor Gene ◽  
Cell Receptor ◽  
Surface Expression ◽  
Receptor Repertoire ◽  
Genes Encoding ◽  
T Cell Receptor Beta ◽  
Gene Transcripts

Abstract Acquisition of mature T cell function and the T cell antigen receptor repertoire occur in the thymus. In an effort to delineate the cascade of events leading to T cell maturation, we analyzed a series of clonal human precursor T cell neoplasms representing early, middle, and late stages of intrathymic differentiation. Rearrangements of the T cell receptor beta and gamma genes appear concurrently and are preceded by surface expression of the 3A1 (CD7) molecule. Subsequent transcription of the beta gene is coordinated with surface expression of T1 (CD5) and T11 (CD2), transcription of T3 delta mRNA, and the appearance of intracellular T3 (CD3) protein. As late events, T alpha gene transcripts appear and, finally, T3, the multichain complex linked to the T cell receptor, is presented on the cell surface. Findings reported here provide a model of the developmental orchestration of genes encoding antigen recognition in human T cells.

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