Involvement of MCAF1-MBD1 complex in hererochromatin formation and nuclear atypia. (2006)

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1. We demonstrate that modification of MBD1 with either SUMO-2/3 or SUMO-1 facilitated the interaction between MBD1 and MCAF1. SUMOs directory interact with human MCAF1-SETDB1 complex. Specific knockdown of either SUMO-2/3 or SUMO-1 induced dissociation of MCAF1, trymethyl-H3-K9, and the HP1 proteins from the MBD1-containing heterofhromatin foci. These findings provide insights into the roles of SUMOylation in the regulation of the MBD1-MCAF1 mediated heterochromatin formation and gene silencing. (J. Biol. Chem. 281:23180-23190)2. We demonstrate that MCAF1 is found to be frequently overexpressed in naturally occurring cancers that orignnate in different tissues. We report that MCAF1 is involved in Sp1-dependent maintenance of telomerase activity in cancer cells. (J.Biol.Chem.284 : 5165-5174)3. We report that the DNA methylation-mediated repressor MBD1 interacts with Ring1b and hPc2, the major components of Polycomb repressive complex. MBD1 and hPC2 cooperate for transcriptional repression of HOXAgene. We also suggest that MBD1 and Polycomb group protains have overlapping roles in epigenetic gene silencing and heterochromatin foci formation through their interaction. (J.Biol.Chem.282 : 16391-400)4. We analyzed the expression level of MCAF1 in cervical cancer tissues. MCAF1 is found to be overexpressed in most of cervical cancer tissues and not to be found in normal cervical tissues. We are now investigating about the possibility of MCAF1 as a maker of cervical cancers.