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

C Courtes, N Lecointe, L Le Cam, F Baudoin, C Sardet, D Mathieu-Mahul

Research output: Contribution to journalArticlepeer-review

Abstract

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 NH2-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'-unstranslated 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.
Original languageEnglish
Pages (from-to)949-958
Number of pages9
JournalJournal of Biological Chemistry
Volume275
Issue number2
DOIs
Publication statusPublished - 14 Jan 2000

Keywords

  • 3T3 Cells
  • 5' Untranslated Regions
  • Animals
  • Base Sequence
  • Basic Helix-Loop-Helix Transcription Factors
  • Binding Sites
  • Cell Line
  • Consensus Sequence
  • DNA-Binding Proteins
  • Endothelium, Vascular
  • Exons
  • Gene Silencing
  • HeLa Cells
  • Helix-Loop-Helix Motifs
  • Humans
  • K562 Cells
  • Leukemia, T-Cell
  • Megakaryocytes
  • Mice
  • Molecular Sequence Data
  • Promoter Regions, Genetic
  • Proto-Oncogene Proteins
  • Regulatory Sequences, Nucleic Acid
  • Repressor Proteins
  • Sequence Alignment
  • Sequence Homology, Nucleic Acid
  • T-Lymphocytes
  • Transcription Factors

Fingerprint

Dive into the research topics of 'Erythroid-specific inhibition of the tal-1 intragenic promoter is due to binding of a repressor to a novel silencer'. Together they form a unique fingerprint.

Cite this