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Br J Haematol. 2005 Oct;131(2):214-8.

Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma.

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1
U.O. Ematologia 2, Centro Trapianti di Midollo, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS Milano, Milan, Italy.

Abstract

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.

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