The WHSC1/MMSET gene, involved in t(4;14)(p16.3;q32) in multiple myeloma, encodes putative isoforms (MMSET I, MMSET II and RE-IIBP) which are thought to be involved in transcription regulation. We investigated their activity in transfected 293T and HeLa cells. Both MMSET I and MMSET II were localised in the nucleus, whereas RE-IIBP showed cytoplasmic and nucleolar staining. MMSET I dose-dependently repressed the transcriptional activity of the promoter region of the thymidine kinase gene, whereas MMSET II and RE-IIBP had no effect. The HDAC inhibitor, trichostatin A, reduced MMSET I repression activity and in vitro co-immunoprecipitation analyses indicated that MMSET I specifically recruits HDAC1 and mSin3b, but not HDAC2 or HDAC4. Our data support the hypothesis that MMSET may act as a transcription regulator; different functions may be associated with distinct isoforms.
|Titolo:||Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma|
|Settore Scientifico Disciplinare:||Settore MED/15 - Malattie del Sangue|
|Data di pubblicazione:||2005|
|Digital Object Identifier (DOI):||10.1111/j.1365-2141.2005.05741.x|
|Appare nelle tipologie:||01 - Articolo su periodico|