Hrp3 controls nucleosome positioning to suppress non-coding transcription in eu- and heterochromatin

Abstract

The positioning of the nucleosome by ATP-dependent remodellers provides the fundamental chromatin environment for the regulation of diverse cellular processes acting on the underlying DNA. Recently, genome-wide nucleosome mapping has revealed more detailed information on the chromatin-remodelling factors. Here, we report that the Schizosaccharomyces pombe CHD remodeller, Hrp3, is a global regulator that drives proper nucleosome positioning and nucleosome stability. The loss of Hrp3 resulted in nucleosome perturbation across the chromosome, and the production of antisense transcripts in the hrp3D cells emphasized the importance of nucleosome architecture for proper transcription. Notably, perturbation of the nucleosome in hrp3 deletion mutant was also associated with destabilization of the DNA-histone interaction and cell cycle-dependent alleviation of heterochromatin silencing. Furthermore, the effect of Hrp3 in the pericentric region was found to be accomplished via a physical interaction with Swi6, and appeared to cooperate with other heterochromatin factors for gene silencing. Taken together, our data indicate that a well-positioned nucleosome by Hrp3 is important for the spatial-temporal control of transcriptionassociated processes.

The Mi-2 Homolog Mit1 Actively Positions Nucleosomes within Heterochromatin To Suppress Transcription

“…Nucleosome positioning in euchromatin in fission yeast is regulated by fellow CHD family chromatin remodeling enzymes, Hrp1 and Hrp3 (38,76). Our data suggest that Mit1 mobilizes nucleosomes within regions of heterochromatin and that DNA sequence may contribute at sites where the loss of Mit1 is most notable.…”

Noncoding Transcription Is a Driving Force for Nucleosome Instability in spt16 Mutant Cells

“…In addition, depletion of histone H3 proteins in S. cerevisiae also results in alterations in nucleosome occupancy and positions at a defined subset of nucleosomes, and interestingly, nucleosomes altered by H3 depletion do not overlap with those altered in cells lacking Nhp6a/Nhp6b (61). Schizosaccharomyces pombe cells lacking chromatin remodeler Chd1 (Hrp3 in S. pombe) exhibit global changes in nucleosomes and production of antisense transcripts (62)(63)(64). Finally, S. pombe yeast cells lacking histone chaperone Spt6 also exhibit dramatic changes in nucleosome positioning and occupancy and increased cryptic transcription (65).…”

Nucleosomal signatures impose nucleosome positioning in coding and noncoding sequences in the genome

“…Chromatin remodelers are multiprotein complexes that use ATP hydrolysis to facilitate the sliding, eviction or histone exchange of nucleosomes (Clapier and Cairns 2009). Remodelers show different specificity and directionality in their mode of action (Stockdale et al 2006;Yen et al 2012), and the removal of some of them, like Hrp3 in Schizosaccharomyces pombe (Hennig et al 2012;Pointner et al 2012;Shim et al 2012) or Isw1 and Chd1 in Saccharomyces cerevisiae (Gkikopoulos et al 2011), results in gross genome-wide alteration of their nucleosomal patterns.…”