Functional regulation of GATA-2 by acetylation

Fumihiko Hayakawa, Masayuki Towatari, Yukiyasu Ozawa, Akihiro Tomita, Martin L. Privalsky, Hidehiko Saito

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Abstract

The transcription factor GATA-2 is expressed in hematopoietic stem and progenitor cells and is functionally implicated in their survival and proliferation. In the present study, we show that GATA-2 exists as an acetylated protein in immature precursor cells, KG1. GATA-2 was acetylated in vitro by p300 and GCN5. We have identified multiple acetylation sites by p300 on GATA-2, which include sites outside the zinc finger domain. We confirmed that GATA-2 acetylation occurred in transiently transfected 293T cells at sites similar to those induced by p300 in vitro. We have successfully shown that acetylation of GATA-2 in vitro increased its DNA-binding activity. In addition, GATA-2 displayed a transcriptional synergism with p300 that was impaired by mutation of each acetylation site. More importantly, each mutation in the acetylation sites of GATA-2 abolished its growth inhibitory effect on an interleukin-3-dependent progenitor, 32D. We conclude that acetylation provides multiple control points for the regulation of GATA-2 function.

Original languageEnglish (US)
Pages (from-to)529-540
Number of pages12
JournalJournal of Leukocyte Biology
Volume75
Issue number3
DOIs
StatePublished - Mar 2004

Fingerprint

Acetylation
Hematopoietic Stem Cells
GATA2 Transcription Factor
Mutation
Interleukin-3
HEK293 Cells
Zinc Fingers
DNA
Growth
In Vitro Techniques
Proteins

Keywords

  • DNA-binding activity
  • GCN5
  • Histone acetyl transferase
  • P300
  • Transcription factor

ASJC Scopus subject areas

  • Cell Biology

Cite this

Hayakawa, F., Towatari, M., Ozawa, Y., Tomita, A., Privalsky, M. L., & Saito, H. (2004). Functional regulation of GATA-2 by acetylation. Journal of Leukocyte Biology, 75(3), 529-540. https://doi.org/10.1189/jlb.0603289

Functional regulation of GATA-2 by acetylation. / Hayakawa, Fumihiko; Towatari, Masayuki; Ozawa, Yukiyasu; Tomita, Akihiro; Privalsky, Martin L.; Saito, Hidehiko.

In: Journal of Leukocyte Biology, Vol. 75, No. 3, 03.2004, p. 529-540.

Research output: Contribution to journalArticle

Hayakawa, F, Towatari, M, Ozawa, Y, Tomita, A, Privalsky, ML & Saito, H 2004, 'Functional regulation of GATA-2 by acetylation', Journal of Leukocyte Biology, vol. 75, no. 3, pp. 529-540. https://doi.org/10.1189/jlb.0603289
Hayakawa F, Towatari M, Ozawa Y, Tomita A, Privalsky ML, Saito H. Functional regulation of GATA-2 by acetylation. Journal of Leukocyte Biology. 2004 Mar;75(3):529-540. https://doi.org/10.1189/jlb.0603289
Hayakawa, Fumihiko ; Towatari, Masayuki ; Ozawa, Yukiyasu ; Tomita, Akihiro ; Privalsky, Martin L. ; Saito, Hidehiko. / Functional regulation of GATA-2 by acetylation. In: Journal of Leukocyte Biology. 2004 ; Vol. 75, No. 3. pp. 529-540.
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