Chromatin immunoselection defines a TAL-1 target gene

Sylvia Cohen-Kaminsky, Leïla Maouche-Chrétien, Luigi Vitelli, Marie Antoinette Vinit, Isabelle Blanchard, Masayugi Yamamoto, Cesare Peschle, Paul Henri Roméo

Research output: Contribution to journalArticlepeer-review

51 Citations (Scopus)

Abstract

Despite the major functions of the basic helix-loop-helix transcription factor TAL-1 in hematopoiesis and T-cell leukemogenesis, no TAL-1 target gene has been identified. Using immunoprecipitation of genomic fragments bound to TAL-1 in the chromatin of murine erythro-leukemia (MEL) cells, we found that 10% of the immunoselected fragments contained a CAGATG or a CAGGTG E-box, followed by a GATA site. We studied one of these fragments containing two E-boxes, CAGATG and CAGGTC, followed by a GATA motif, and showed that TAL-1 binds to the CAGGTG E-box with an affinity modulated by the CAGATG or the GATA site, and that the CAGGTG-GATA motif exhibits positive transcriptional activity in MEL but not in HeLa cells. This immunoselected sequence is located within an intron of a new gene co-expressed with TAL-1 in endothelial and erythroid cells, but not expressed in fibroblasts or adult liver where no TAL-1 mRNA was detected. Finally, in vitro differentiation of embryonic stem cells towards the erythro/megakaryocytic pathways showed that the TAL-1 target gene expression followed TAL-1 and GATA-1 expression. These results establish that TAL-1 is likely to activate its target genes through a complex that binds an E-box-GATA motif and define the first gene regulated by TAL-1.

Original languageEnglish
Pages (from-to)5151-5160
Number of pages10
JournalEMBO Journal
Volume17
Issue number17
DOIs
Publication statusPublished - 1998 Sep 1

Keywords

  • Chromatin immunoprecipitation
  • GATA motif
  • Hematopoiesis
  • MEL cells
  • TAL-1 target genes

ASJC Scopus subject areas

  • Neuroscience(all)
  • Molecular Biology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Immunology and Microbiology(all)

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