Cross talk between retinoic acid signaling and transcription factor GATA-2

Shinobu Tsuzuki, Kenji Kitajima, Toru Nakano, Annegret Glasow, Arthur Z Zelent, Tariq Enver

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

All-trans-retinoic acid (RA) stimulates differentiation of normal hematopoietic progenitors and acute myeloid leukemia cells. GATA-2 is a transcription factor expressed in early progenitor cells and implicated in the control of the fate of hematopoietic stem cells and progenitor cells. We have investigated the possibility that the GATA and nuclear hormone receptor pathways are functionally linked through direct protein-protein interaction. Here we demonstrate that in human myeloid KG1 cells, RA receptor alpha (RARα), the major RAR expressed in hematopoietic cells, associates with GATA-2. This association is mediated by the zinc fingers of GATA-2 and the DNA-binding domain of RARα. As a consequence of this interaction, RARα is tethered to the DNA sites that are recognized and bound by GATA-2 and the transcriptional activity of GATA-2 becomes RA responsive. The RA responsiveness of GATA-dependent transcription is eliminated by expression of either a dominant negative form of RARα or a GATA-2 mutant that fails to interact with RARα. Overexpression of RXRα inhibits RARα binding to the GATA-2-DNA complex, thus resulting in attenuation of the effects of RARα on GATA-2 activity. In addition, inhibition by RA of GATA-2-dependent hematopoietic colony formation in an embryonic stem cell model of hematopoietic differentiation provided biological evidence for functional cross talk between RA and GATA-2-dependent pathways.

Original languageEnglish (US)
Pages (from-to)6824-6836
Number of pages13
JournalMolecular and Cellular Biology
Volume24
Issue number15
DOIs
StatePublished - Aug 2004
Externally publishedYes

Fingerprint

GATA2 Transcription Factor
Tretinoin
Myeloid Cells
DNA
Stem Cells
Zinc Fingers
Embryonic Stem Cells
Cytoplasmic and Nuclear Receptors
Hematopoietic Stem Cells
Acute Myeloid Leukemia
Proteins
Transcription Factors

ASJC Scopus subject areas

  • Molecular Biology
  • Genetics
  • Cell Biology

Cite this

Tsuzuki, S., Kitajima, K., Nakano, T., Glasow, A., Zelent, A. Z., & Enver, T. (2004). Cross talk between retinoic acid signaling and transcription factor GATA-2. Molecular and Cellular Biology, 24(15), 6824-6836. https://doi.org/10.1128/MCB.24.15.6824-6836.2004

Cross talk between retinoic acid signaling and transcription factor GATA-2. / Tsuzuki, Shinobu; Kitajima, Kenji; Nakano, Toru; Glasow, Annegret; Zelent, Arthur Z; Enver, Tariq.

In: Molecular and Cellular Biology, Vol. 24, No. 15, 08.2004, p. 6824-6836.

Research output: Contribution to journalArticle

Tsuzuki, S, Kitajima, K, Nakano, T, Glasow, A, Zelent, AZ & Enver, T 2004, 'Cross talk between retinoic acid signaling and transcription factor GATA-2', Molecular and Cellular Biology, vol. 24, no. 15, pp. 6824-6836. https://doi.org/10.1128/MCB.24.15.6824-6836.2004
Tsuzuki, Shinobu ; Kitajima, Kenji ; Nakano, Toru ; Glasow, Annegret ; Zelent, Arthur Z ; Enver, Tariq. / Cross talk between retinoic acid signaling and transcription factor GATA-2. In: Molecular and Cellular Biology. 2004 ; Vol. 24, No. 15. pp. 6824-6836.
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