Article Dans Une Revue Journal of Biological Chemistry Année : 2000

Erythroid-specific inhibition of the tal-1 intragenic promoter is due to binding of a repressor to a novel silencer

Résumé

The basic helix-loop-helix tal-1 gene plays a key role in hematopoiesis, and its expression is tightly controlled through alternative promoters and complex interactions of cis-acting regulatory elements. tal-1 is not expressed in normal T cells, but its transcription is constitutive in a large proportion of human T cell leukemias. We have previously described a downstream initiation of tal-1 transcription specifically associated with a subset of T cell leukemias that leads to the production of NH(2)-truncated TAL-1 proteins. In this study, we characterize the human promoter (promoter IV), embedded within a GC-rich region in exon IV, responsible for this transcriptional activity. The restriction of promoter IV usage is assured by a novel silencer element in the 3'-untranslated region of the human gene that represses its activity in erythroid but not in T cells. The silencer activity is mediated through binding of a tissue-specific nuclear factor to a novel protein recognition motif (designated tal-RE) in the silencer. Mutation of a single residue within the tal-RE abolishes both specific protein binding and silencing activity. Altogether, our results demonstrate that the tal-1 promoter IV is actively repressed in cells of the erythro-megakaryocytic lineage and that this repression is released in leukemic T cells, resulting in the expression of the tal-1 truncated transcript.

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hal-02196811 , version 1 (27-05-2021)

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C. Courtes, N. Lecointe, L. Le Cam, Fulbert Baudoin, C. Sardet, et al.. Erythroid-specific inhibition of the tal-1 intragenic promoter is due to binding of a repressor to a novel silencer. Journal of Biological Chemistry, 2000, 275 (2), pp.949-958. ⟨10.1074/jbc.275.2.949⟩. ⟨hal-02196811⟩
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