CTCF binding resulting in enhancer stimulation of IGF2 expression and H19 silencing. Recent studies using chromosome conformation capture have shown that long range allele-specific interactions constitute part of the insulation mechanism but our understanding of these interactions is still incomplete. A complex three-dimensional, multiple-loop model organized by the CTCF-ICR complex on the maternal allele has been recently proposed and both intra and inter-chromosomal interactions have been shown to involve the H19 ICR. Loss of imprinting concurrent to hypomethylation at the H19/IGF2 intergenic region has been observed in a limited number of primary synovial sarcomas and SYT-SSX expression has been shown to induce IGF2 in immortalized MRC5 fibroblasts and HEK 293 cells. In the latter case, IGF2 induction could be attributed to epigenetic mechanisms: hypermethylation was observed at the H19/IGF2 intergenic region and enrichment of histone marks associated with active chromatin was observed at the IGF2 promoter. More recently, epigenetic effects of SYT-SSX on other targets have been reported. Thus, down-regulation of EGR1 by SYT-SSX expression in HEK 293 cells was shown to occur via histone modifications and recruitment of polycomb proteins to the EGR1 promoter. Finally the histone deacetylase inhibitor FK228 has been reported to block synovial sarcoma cell growth both in vitro and in vivo. Most of these studies were conducted using cell lines that may have acquired significant modifications of their epigenetic status both during transformation and during prolonged cell culture. They were therefore unlikely to fully recapitulate the biology of primary in vivo tumor development. Thus, despite these potentially relevant insights, it remains unclear DCVC (E-isomer) whether the epigenetic effects of SYT-SSX are required for tumor development, maintenance and/or other biological properties of synovial sarcoma. The precise mechanism of epigenetic deregulation by the synovial sarcoma fusion protein has yet to be defined as do the epigenetic features that may render primary cells permissive for SYT-SSX functions and order 940929-33-9 potential oncogenic properties. To address these issues, we introduc
