Transcription repression activity is associated with the type I isoform of the MMSET gene involved in t(4;14) in multiple myeloma.
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.
Todoerti
Katia
K
U.O. Ematologia 2, Centro Trapianti di Midollo, Dipartimento di Scienze Mediche, Università degli Studi di Milano, Ospedale Maggiore IRCCS Milano, Milan, Italy.
Ronchetti
Domenica
D
Agnelli
Luca
L
Castellani
Stefano
S
Marelli
Silvia
S
Deliliers
Giorgio Lambertenghi
GL
Zanella
Alberto
A
Lombardi
Luigia
L
Neri
Antonino
A
D002352:Carrier Proteins / Q000235:genetics*; D002460:Cell Line; D002883:Chromosomes, Human, Pair 14; D002894:Chromosomes, Human, Pair 4; D017353:Gene Deletion; D015972:Gene Expression Regulation, Neoplastic; D005809:Genes, Regulator; D006367:HeLa Cells; D011495:Histone-Lysine N-Methyltransferase; D006801:Humans; D009101:Multiple Myeloma / Q000235:genetics*; D020033:Protein Isoforms / Q000235:genetics; D017434:Protein Structure, Tertiary; D012097:Repressor Proteins / Q000235:genetics*; D014158:Transcription, Genetic
D002352:Carrier Proteins; D020033:Protein Isoforms; D012097:Repressor Proteins; D011495:Histone-Lysine N-Methyltransferase; C419586:NSD2 protein, human