In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediatedtranscriptional repression

Citation
F. Kihara-negishi et al., In vivo complex formation of PU.1 with HDAC1 associated with PU.1-mediatedtranscriptional repression, ONCOGENE, 20(42), 2001, pp. 6039-6047
Citations number
48
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Onconogenesis & Cancer Research
Journal title
ONCOGENE
ISSN journal
0950-9232 → ACNP
Volume
20
Issue
42
Year of publication
2001
Pages
6039 - 6047
Database
ISI
SICI code
0950-9232(20010920)20:42<6039:IVCFOP>2.0.ZU;2-8
Abstract
We previously reported that overexpression of PU.1, a member of the Ets fam ily of transcription factors, induces differentiation inhibition and apopto sis associated with c-Myc down-regulation in murine erythroleukemia (MEL) c ells. To understand the molecular mechanism by which c-Myc is down-regulate d due to overexpression of PU.1, we performed luciferase reporter assays us ing 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 domai n 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-m ediated transcriptional repression. Instead, it was found that the C-termin al 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 v itro and in vivo. Our results suggest that overexpression of PU.1 induces t ranscriptional repression in several gene promoters including the c-myc pro moter which may be mediated by its complex formation with HDACs.