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- Title
In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediated transcriptional repression.
- Authors
Kihara-Negishi, Fumiko; Yamamoto, Hitomi; Suzuki, Mitsuhiro; Yamada, Toshiyuki; Sakurai, Takuya; Tamura, Takaaki; Oikawa, Tsuneyuki
- Abstract
We previously reported that overexpression of PU.1, a member of the Ets family of transcription factors, induces differentiation inhibition and apoptosis associated with c-Myc down-regulation in murine erythroleukemia (MEL) cells. To understand the molecular mechanism by which c-Myc is down-regulated due to overexpression of PU.1, we performed luciferase reporter assays using the mouse c-myc promoter. PU.1 repressed the activities of not only the c-myc promoter but also several other promoters. Experiments with deletion mutants of PU.1 revealed that the C-terminal region spanning amino acids (aa) 123–272 including the PEST and ETS domains but not the activation domain was sufficient for this transcriptional repression. It was unlikely that the repression was due to sequestration of a limited amount of CBP/p300 nor pCAF, because overexpression of these co-activators did not relieve PU.1-mediated transcriptional repression. Instead, it was found that the C-terminal aa 101–272 of PU.1 formed a complex with mSin3A and HDAC1 in vivo, which was speculated to be associated with the repression. The C-terminal region of PU.1 also formed a complex with the basic transcription factor TBP in vitro and in vivo. Our results suggest that overexpression of PU.1 induces transcriptional repression in several gene promoters including the c-myc promoter which may be mediated by its complex formation with HDACs. Oncogene (2001) 20, 6039–6047.
- Subjects
TRANSCRIPTION factors; APOPTOSIS; MOUSE leukemia
- Publication
Oncogene, 2001, Vol 20, Issue 42, p6039
- ISSN
0950-9232
- Publication type
Article
- DOI
10.1038/sj.onc.1204756