The B-WICH chromatin-remodelling complex regulates RNA polymerase III transcription by promoting Max-dependent c-Myc binding.

Fatemeh Sadeghifar,Stefanie Böhm,Anna Vintermist,Ann-Kristin Östlund Farrants

doi:10.1093/nar/gkv312

Abstract

The chromatin-remodelling complex B-WICH, comprised of William syndrome transcription factor, the ATPase SNF2h and nuclear myosin, specifically activates RNA polymerase III transcription of the 5S rRNA and 7SL genes. However, the underlying mechanism is unknown. Using high-resolution MN walking we demonstrate here that B-WICH changes the chromatin structure in the vicinity of the 5S rRNA and 7SL RNA genes during RNA polymerase III transcription. The action of B-WICH is required for the binding of the RNA polymerase machinery and the regulatory factors c-Myc at the 5S rRNA and 7SL RNA genes. In addition to the c-Myc binding site at the 5S genes, we have revealed a novel c-Myc and Max binding site in the intergenic spacer of the 5S rDNA. This region also contains a region remodelled by B-WICH. We demonstrate that c-Myc binds to both sites in a Max-dependent way, and thereby activate transcription by acetylating histone H3. 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.

Highlights

Transcription by RNA polymerase III (RNA pol III) in eukaryotic cells is closely associated with cell growth and proliferation
This study demonstrates that chromatin is an important regulator of RNA pol III transcription and that chromatinremodelling complexes are required to alter the chromatin structure in the vicinity of the genes for transcriptional activation
We have studied the order of events upon transcriptional activation of 5S rRNA and 7SL RNA genes and demonstrated that chromatin remodelling is required early in the process

Summary

Introduction

Transcription by RNA polymerase III (RNA pol III) in eukaryotic cells is closely associated with cell growth and proliferation. RNA pol III genes are regulated by nutrients and cellular stress, as well as by proliferative signals generated throughout the cell cycle and differentiation [1,2]. Several transcription factors, such as c-Myc and c-Jun, and signalling pathways, such as the MAP kinase pathway, activate these genes [3,4,5]. The proliferative regulator c-Myc binds directly to the TFIIIB component Brf (or Brf on the snU6 RNA genes) [12,13,14,15,16], in a Max-independent manner in RNA pol III transcription. In RNA pol II transcription, cMyc binds to a DNA-binding site, an E-box, as c-Myc-Max dimers at promoter and enhancer regions [17]

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