SYT associates with human SNF/SWI complexes and the C-terminal region of its fusion partner SSX1 targets histones.
A global transcriptional co-activator, the SNF/SWI complex, has been characterized as a chromatin remodeling factor that enhances accessibility of the transcriptional machinery to DNA within a repressive chromatin structure. On the other hand, mutations in some human SNF/SWI complex components have been linked to tumor formation. We show here that SYT, a partner protein generating the synovial sarcoma fusion protein SYT-SSX, associates with native human SNF/SWI complexes. The SYT protein has a unique QPGY domain, which is also present in the largest subunits, p250 and the newly identified homolog p250R, of the corresponding SNF/SWI complexes. The C-terminal region (amino acids 310-387) of SSX1, comprising the SSX1 portion of the SYT-SSX1 fusion protein, binds strongly to core histones and oligonucleosomes in vitro and directs nuclear localization of a green fluorescence protein fusion protein. Experiments with serial C-terminal deletion mutants of SSX1 indicate that these properties map to a common region and also correlate with the previously demonstrated anchorage-independent colony formation activity of SYT-SSX in Rat 3Y1 cells. These data suggest that SYT-SSX interferes with the function of either the SNF/SWI complexes or another SYT-interacting co-activator, p300, by changing their targeted localization or by directly inhibiting their chromatin remodeling activities.
Kato
Hiroyuki
H
Laboratory of Biochemistry and Molecular Biology and Laboratory of Mass Spectrometry and Gaseous Ion Chemistry, The Rockefeller University, New York, New York 10021, USA. hykato@nih.go.jp
Tjernberg
Agneta
A
Zhang
Wenzhu
W
Krutchinsky
Andrew N
AN
An
Woojin
W
Takeuchi
Tamotsu
T
Ohtsuki
Yuji
Y
Sugano
Sumio
S
de Bruijn
Diederik R
DR
Chait
Brian T
BT
Roeder
Robert G
RG
D000595:Amino Acid Sequence; D002460:Cell Line; D002467:Cell Nucleus / Q000378:metabolism; D002843:Chromatin / Q000737:chemistry; D004591:Electrophoresis, Polyacrylamide Gel; D017353:Gene Deletion; D005982:Glutathione Transferase / Q000378:metabolism; D006367:HeLa Cells; D006657:Histones / Q000378:metabolism; D006801:Humans; D015151:Immunoblotting; D008957:Models, Genetic; D008969:Molecular Sequence Data; D016297:Mutagenesis, Site-Directed; D010957:Plasmids / Q000378:metabolism; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry* / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012097:Repressor Proteins; D014157:Transcription Factors / Q000737:chemistry*; D014158:Transcription, Genetic
D002843:Chromatin; D006657:Histones; D011506:Proteins; D011518:Proto-Oncogene Proteins; D011993:Recombinant Fusion Proteins; D012097:Repressor Proteins; C093961:SS18 protein, human; D014157:Transcription Factors; D005982:Glutathione Transferase; C071570:SNF1-related protein kinases; D017346:Protein Serine-Threonine Kinases