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

Open Access

30 September 2005

journal article
Published by Wiley in British Journal of Haematology

Vol. 131 (2) , 214-218
https://doi.org/10.1111/j.1365-2141.2005.05741.x

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.

Keywords

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