Abstract
Coactivator and corepressor (cofactors) are essential for the transcriptional regulation by nuclear receptor (NR). Coactivator possesses intrinsic histone acetylase (HAT) activity and corepressor is associated with histone deacetylase (HDAC). These enzyme activities are indispensable for the function of these cofactors, and also for modulation of chromatin structures, or epigenetic regulation. Recently, we have shown that dysregulation of the HAT activity causes human diseases such as Rubinstein-Taybi Syndrome (RTS) and Huntington's disease.Our present efforts are to identify the roles of HAT activity in eukaryotic transcriptional regulation. Recently we have found an RNA-binding protein, TLS (translocated in liposarcoma)/FUS, which has potent inhibitory effect on the HAT activity of CREB-binding protein (CBP). This inhibitory molecule has a regulatory role in a CREB-dependent transcription system. Unexpectedly, specific RNA sequences stimulate the inhibitory activity of TLS. Such RNA sequence exists at 94% of coding regions of human genome. The specific RNAs form guanine (G) quartet structures in a K+-dependent manner. This structure enhanced binding of the RNAs to TLS. Addition of the RNAs in HAT assay of CBP with TLS resulted in more efficient inhibition to the HAT activity. These results have demonstrated that the RNAs with G-quartet structure function as ligands for TLS and that the TLS-RNA complex is a potent repressor for the CREB-dependent transcriptional systems, suggesting that TLS mediates RNA-dependent transcriptional repression. [J Physiol Sci. 2006;56 Suppl:S2]
