Microspherule protein 1, Mi-2β, and RET finger protein associate in the nucleolus and up-regulate ribosomal gene transcription

The nucleolus is the site of ribosomal DNA ( rDNA) transcription and ribosome production. In exploring the role of nucleolar protein MCRS1 ( microspherule protein1)/MSP58 ( 58-kDa microspherule protein), we found that Mi-2 beta, a component of a nucleosome remodeling and deacetylase ( NuRD) complex, RET finger protein ( RFP), and upstream binding factor ( UBF) were associated with MCRS1. Yeast two-hybrid assays revealed that MCRS1 bound to the ATPase/helicase region of Mi-2 beta and the coiled-coil region of RFP. Interestingly, confocal microscopic analyses revealed the co-localization of MCRS1, Mi-2 beta, RFP, and the rRNA transcription factor UBF in the nucleoli. We also found that MCRS1, Mi-2 beta, and RFP were associated with rDNA using a chromatin immunoprecipitation assay. Finally, we showed that MCRS1, Mi-2 beta, and RFP up-regulated transcriptional activity of the rDNA promoter and that ribosomal RNA transcription was repressed when MCRS1, Mi-2 beta, and RFP expression was reduced using siRNA. These results indicated that Mi-2 beta and RFP, known to be involved in transcriptional repression in the nucleus, co-localize with MCRS1 in the nucleolus and appear to activate the rRNA transcription.