A pentamer transcriptional complex including tal-1 and retinoblastoma protein downmodulates c-kit expression in normal erythroblasts

Luigi Vitelli, Gianluigi Condorelli, Valentina Lulli, Trang Hoang, Luisella Luchetti, Carlo M. Croce, Cesare Peschle

Research output: Contribution to journalArticlepeer-review

Abstract

Human proerythroblasts and early erythroblasts, generated in vitro by normal adult progenitors, contain a pentamer protein complex comprising the tal-1 transcription factor heterodimerized with the ubiquitous E2A protein and linked to Lmo2, Ldbl, and retinoblastoma protein (pRb). The pentamer can assemble on a consensus tal-1 binding site. In the pRb- SAOS-2 cell line transiently transfected with a reporter plasmid containing six tal-1 binding site, pRb enhances the transcriptional activity of tal-1-E12-Lmo2 and tal-1- E12Lmo2-Ldbl complexes but not that of a tal-1-E12 heterodimer. We explored the functional significance of the pentamer in erythropoiesis, specifically, its transcriptional effect on the c-kit receptor, a tal-1 target gene stimulating early hematopoietic proliferation downmodulated in erythroblasts. In TF1 cells, the pentamer decreased the activity of the reporter plasmid containing the c-kit proximal promoter with two inverted E box-2 type motifs. In SAOS-2 cells the pentamer negatively regulates (i) the activity of the reporter plasmid containing the proximal human c-kit promoter and (ii) endogenous c-kit expression. In both cases pRb significantly potentiates the inhibitory effect of the tal-1-E12-Lmo2-Ldbl tetramer. These data indicate that this pentameric complex assembled in maturing erythroblasts plays an important regulatory role in c-kit downmodulation; hypothetically, the complex may regulate the expression of other critical erythroid genes.

Original languageEnglish
Pages (from-to)5330-5342
Number of pages13
JournalMolecular and Cellular Biology
Volume20
Issue number14
DOIs
Publication statusPublished - Jul 2000

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

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