Impaired repressor activity and biological functions of PU.1 in MEL cells induced by mutations in the acetylation motifs within the ETS domain
Abstract
PU.1, a hematopoietic Ets transcription factor, is required for development of the lymphoid and myeloid lineages. We have previously shown that PU.1 functions as both a transcriptional activator and repressor through complex formation with CBP/p300 and HDAC1/mSin3A/MeCP2, respectively. To determine whether modification of PU.1 is responsible for switching its association between co-activators and co-repressors, we examined whether acetylation regulates the physical and functional activities of PU.1. PU.1 was acetylated in vivo and its repressor activity was reduced when the putative acetylation motifs in the Ets domain were mutated. The mutant cooperated with CBP similar to wild type PU.1, but insufficiently with GATA-1 and mSin3A. Whereas overexpression of wild type PU.1 induced differentiation block, growth inhibition, and apoptotic cell death in MEL erythroleukemia cells as we reported previously, overexpression of the mutant-acetylation motif PU.1 did not. Taken together, our data suggest that acetylation might regulate the biological functions of PU.1 in erythroid cells.
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BackgroundPU.1, a Versatile Transcription Factor and a Suppressor of Myeloid Leukemia
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“Acetylation has been reported to enhance transcriptional activity, potentially by promoting cofactor recruitment or increasing chromatin accessibility at target loci [58,59].”
- Authors
- Kihara-Negishi, F., Suzuki, M., Yamada, T., Sakurai, T., & Oikawa, T.
- Affiliations
- Sasaki Institute (JP)
- Corresponding author
- Oikawa, Tsuneyuki
- Venue
- Biochemical and Biophysical Research Communications
- Publisher
- Elsevier BV
- Published
- 2005-09
- Volume
- 335
- Issue
- 2
- Pages
- 477-484
- ISSN
- 0006-291X (ISSN-L)
- OpenAlex
- W2043394015
- Cited by
- 13
- References
- 28
- Citations by year
- 2026: 2 · 2020: 1 · 2018: 1 · 2017: 1 · 2014: 2 · 2013: 1 · 2012: 3
- FWCI
- 0.12
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical and Biophysical Research Communications (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Health Sciences › Medicine › Hematology › Hematopoietic Stem Cell Transplantation
- Keywords
- PU.1, ETS transcription factors, protein acetylation, CBP/p300, GATA-1, erythroid differentiation, apoptosis
- MeSH terms
- Proto-Oncogene Protein Spi-1, Acetylation, Animals, Cell Differentiation, Cell Line, DNA-Binding Proteins, Glutathione Transferase, Humans, Luciferases
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