The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.
Bottom Line: The novel binding patterns of c-Myc and Max link transcription of 5S rRNA to the Myc/Max/Mxd network.Since B-WICH acts prior to c-Myc and other factors, we propose a model in which the B-WICH complex is required to maintain an open chromatin structure at these RNA polymerase III genes.This is a prerequisite for the binding of additional regulatory factors.
Affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden.Show MeSH
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Mentions: WSTF knock-down had a greater effect on the factor binding at the 5S rDNA locus than c-Myc or Max knock-down. This led us to investigate the order of events between WSTF and c-Myc in transcriptional activation. To determine whether c-Myc knock-down and the subsequent reduction of histone H3 acetylation lead to a similar remodelling of the chromatin structure as that observed in WSTF KD cells, we performed high-resolution MNase walking. In contrast to WSTF knock-down (Figure 2C), c-Myc knock-down did not result in a changed chromatin structure at the 5S rDNA (Figure 8A). This clearly demonstrates that the B-WICH acts at a step prior to c-Myc. This is further supported by the finding that the binding of the B-WICH complex components WSTF and SNF2h was not compromised in c-Myc KD cells (Figure 8B). WSTF and SNF2h were also present at the 5S rDNA locus in cells treated with the compound 10058-F4 and in Brf1 KD cells (Supplementary Figure S6D). We conclude that the B-WICH complex acts prior to c-Myc in the activation of 5S rRNA transcription. We propose a model in which B-WICH is required for the remodelling of chromatin such that a site, most likely an E-box at the 5S rDNA, becomes accessible for the c-Myc-Max complex (Figure 8C). The c-Myc-Max complex subsequently recruits further factors, such as HATs, to obtain the H3 acetylation that is necessary for transcriptional activation.
Affiliation: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Sweden.