Chromatin remodelling at promoters suppresses antisense transcription

Abstract

Chromatin allows the eukaryotic cell to package its DNA efficiently. To understand how chromatin structure is controlled across the Saccharomyces cerevisiae genome, we have investigated the role of the ATP-dependent chromatin remodelling complex Isw2 in positioning nucleosomes. We find that Isw2 functions adjacent to promoter regions where it repositions nucleosomes at the interface between genic and intergenic sequences. Nucleosome repositioning by Isw2 is directional and results in increased nucleosome occupancy of the intergenic region. Loss of Isw2 activity leads to inappropriate transcription, resulting in the generation of both coding and noncoding transcripts. Here we show that Isw2 repositions nucleosomes to enforce directionality on transcription by preventing transcription initiation from cryptic sites. Our analyses reveal how chromatin is organized on a global scale and advance our understanding of how transcription is regulated.

Thermodynamics of Intragenic Nucleosome Ordering

“…This is consistent with the fact that chromatin regulators may control the interbarrier distance L and in turn the distance L (; L À188 bp) via the statistical ordering imposed by nucleosome excluding barriers. Note that in the precise case of Iswi2 remodeling (Whitehouse et al 2007), we did not obtain conclusive results concerning the crystal/bi-stable nature of the target genes (data not shown). When compared to crystal genes, bi-stable genes are thus highly plastic, with a wide dynamic range of expression level as the signature of a more dynamic and regulated chromatin structure.…”

Nucleosome Remodeling and Epigenetics

“…Genome-wide chromatin remodeling by ISW2 near promoters and in coding regions increases nucleosome density and enforces the accuracy of transcription (Yadon et al 2010). More specifically, the isw2 and isw1 complexes contribute to the positioning of nucleosomes in intergenic regions or in the middle of genes, respectively, which suppresses cryptic, antisense transcription that would otherwise pose a risk of interfering with sense transcription (Whitehouse et al 2007;Tirosh et al 2010). The positioning and phasing of nucleosomes around transcription start sites in yeast, which frequently carry information in the form of histone variants and specific modifications, are brought about by the RSC complex in S. cerevisiae Zhang et al 2011).…”

Stable and dynamic nucleosome states during a meiotic developmental process

“…Conceivably, under energy-rich growth conditions, nucleosomes may be actively placed in thermodynamically less favorable positions at carbon-responsive genes, a concept whose mechanism has been developed elsewhere (Whitehouse et al 2007). Under comparatively lower energy states in carbon-depleted media, this Figure 6.…”