RSF Governs Silent Chromatin Formation via Histone H2Av Replacement

Human remodeling and spacing factor (RSF) consists of a heterodimer of Rsf-1 and hSNF2H, a counterpart of Drosophila ISWI. RSF possesses not only chromatin remodeling activity but also chromatin assembly activity in vitro. While no other single factor can execute the same activities as RSF, the biological significance of RSF remained unknown. To investigate the in vivo function of RSF, we generated a mutant allele of Drosophila Rsf-1 (dRsf-1). The dRsf-1 mutant behaved as a dominant suppressor of position effect variegation. In dRsf-1 mutant, the levels of histone H3K9 dimethylation and histone H2A variant H2Av were significantly reduced in an euchromatic region juxtaposed with heterochromatin. Furthermore, using both genetic and biochemical approaches, we demonstrate that dRsf-1 interacts with H2Av and the H2Av-exchanging machinery Tip60 complex. These results suggest that RSF contributes to histone H2Av replacement in the pathway of silent chromatin formation

The Role of Nucleosomes in Epigenetic Gene Regulation

Chromatin is a dynamic and highly organised structure that plays a role in all aspects of chromatin biology and controls access to DNA. The basic repeating unit of chromatin is the nucleosome, an octamer of histone proteins wrapped around twice with DNA. Transcriptional gene regulation is largely controlled by the epigenetic regulation of the nucleosome, both through the position of the nucleosome in the DNA and chemical modifications to the histone proteins within the nucleosome core. In this chapter, we discuss the role of the nucleosome in controlling gene regulation at promoters, enhancers and in gene bodies. We also discuss the role of bivalent chromatin and asymmetric nucleosomes at these elements. While the focus of this chapter is on transcriptional regulation, many of the concepts also extend to other aspects of chromatin biology including DNA repair and replication