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 language | English |
|---|---|
| Pages (from-to) | 529-540 |
| Number of pages | 12 |
| Journal | Journal of Leukocyte Biology |
| Volume | 75 |
| Issue number | 3 |
| DOIs | |
| Publication status | Published - 01-03-2004 |
| Externally published | Yes |
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All Science Journal Classification (ASJC) codes
- Immunology and Allergy
- Immunology
- Cell Biology
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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, 01.03.2004, p. 529-540.Research output: Contribution to journal › Article
TY - JOUR
T1 - Functional regulation of GATA-2 by acetylation
AU - Hayakawa, Fumihiko
AU - Towatari, Masayuki
AU - Ozawa, Yukiyasu
AU - Tomita, Akihiro
AU - Privalsky, Martin L.
AU - Saito, Hidehiko
PY - 2004/3/1
Y1 - 2004/3/1
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=1542343945&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=1542343945&partnerID=8YFLogxK
U2 - 10.1189/jlb.0603289
DO - 10.1189/jlb.0603289
M3 - Article
C2 - 15001660
AN - SCOPUS:1542343945
VL - 75
SP - 529
EP - 540
JO - Journal of Leukocyte Biology
JF - Journal of Leukocyte Biology
SN - 0741-5400
IS - 3
ER -