Regulation of RNA polymerase I and RNA polymerase III transcription by the chromatin remodelling complex B-WICH

Abstract: Ribosomal biogenesis is an important process which determines the rate of cell growth and is involved in cell response to proliferation, differentiation, cellular nutritional state and stress. The chromatin remodelling complex B-WICH composed of WSTF, SNF2h and NM1 is involved in transcription by the RNA pol I and RNA pol III. In this study I investigated the mechanism by which the B-WICH complex modulates the RNA pol I and RNA pol III transcription. I showed that B-WICH binds to the 45S genes, 5S rRNA and 7SL RNA genes, and remodels the chromatin. The remodelling at the 45S genes occurs at the promoter, leading higher accessibility to histone acetyltransferases, such as PCAF and p300. In the RNA pol III transcription, the chromatin outside of the gene is more open, leading to binding of c-Myc, with the subsequent recruitment of histone acetylation resulting in H3-Ac. The importance of the chromatin remodelling around the genes was particularly clear in WSTF knock-down cells, in which the binding of RNA pol III and auxiliary transcription factors at the 5S rRNA and 7SL RNA gene promoters were totally abolished. I concluded that B-WICH functions in a similar manner on both RNA pol I and RNA pol III genes, remodels chromatin locally at the promoter and around the genes, which allows other factors to bind. I also investigated the role of B-WICH in the control of RNA pol I transcription, in the cell cycle and in response to glucose/energy status. My results showed that the B-WICH complex disassembled in prophase, and reassembled at G1. WSTF is hyperphosphorylated in mitosis, and with the dephosphorylation at the end of telophase, the SNF2h and NM1 bind to the WSTF. A reduction of the association of the B-WICH complex is seen in cells treated with inhibitors of different signalling pathways. Furthermore, during glucose deprivation, the level of B-WICH decreases at the RNA pol I promoter. These results demonstrate that the chromatin remodelling complex B-WICH is important in the transcription of RNA pol I and RNA pol III genes, as maintaining the chromatin state in an active configuration.