Distinct Modes of Regulation by Chromatin Encoded through Nucleosome Positioning Signals

Abstract

The detailed positions of nucleosomes profoundly impact gene regulation and are partly encoded by the genomic DNA sequence. However, less is known about the functional consequences of this encoding. Here, we address this question using a genome-wide map of ∼380,000 yeast nucleosomes that we sequenced in their entirety. Utilizing the high resolution of our map, we refine our understanding of how nucleosome organizations are encoded by the DNA sequence and demonstrate that the genomic sequence is highly predictive of the in vivo nucleosome organization, even across new nucleosome-bound sequences that we isolated from fly and human. We find that Poly(dA:dT) tracts are an important component of these nucleosome positioning signals and that their nucleosome-disfavoring action results in large nucleosome depletion over them and over their flanking regions and enhances the accessibility of transcription factors to their cognate sites. Our results suggest that the yeast genome may utilize these nucleosome positioning signals to regulate gene expression with different transcriptional noise and activation kinetics and DNA replication with different origin efficiency. These distinct functions may be achieved by encoding both relatively closed (nucleosome-covered) chromatin organizations over some factor binding sites, where factors must compete with nucleosomes for DNA access, and relatively open (nucleosome-depleted) organizations over other factor sites, where factors bind without competition.

Chromatin-dependent Transcription Factor Accessibility Rather than Nucleosome Remodeling Predominates during Global Transcriptional Restructuring in Saccharomyces cerevisiae

“…In agreement with this inference, previous studies mapping genome-wide nucleosome positions at steady state have discovered a strong enrichment of predicted transcription factor binding sites in NDRs (Yuan et al, 2005;Lee et al, 2007;Morse, 2007;Field et al, 2008). Extending these studies, we found that gene promoters with an accessible transcription factor binding motif are significantly more likely to be regulated like known targets of that transcription factor than promoters where the motif is occluded by a nucleosome.…”

“…These preset promoters tend to be underrepresented for TATA boxes and tend to have a strong nucleosome-depleted region at a stereotypical position relative to the transcriptional start site, a promoter architecture that has been termed "type II" (Field et al, 2008). Previous work has characterized TATA-less promoters as enriched in constitutively expressed housekeeping genes (Basehoar et al, 2004), but the work reported here clearly demonstrates that individual TATA-less preset promoters are capable of dramatic gene expression changes.…”

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

“…We employed a statistical model inspired by that of Segal et al (13), Field et al (16), and Kaplan et al (18). However, whereas their models are trained on experimental data, we employed this type of model to create a computationally inexpensive approximation to the theoretical nucleosome model recently published in Eslami-Mossallam et al (4).…”

“…Around the TSS of Saccharomyces cerevisiae (baker's yeast), nucleosomes have been found to be depleted on average, both in vitro and in vivo (12)(13)(14)(15)(16)(17)(18). The persistence of this depletion in vitro, in the absence of active remodeling, identifies the sequence preferences of nucleosomes as the dominant cause.…”

“…The persistence of this depletion in vitro, in the absence of active remodeling, identifies the sequence preferences of nucleosomes as the dominant cause. Those preferences have been measured and utilized in various models to explain the observed nucleosome depletion (15,16,(18)(19)(20). These nucleosome-depleted regions (NDRs) in gene promoters are thought to be encoded into the genomic sequence to allow RNA polymerases more ready access to the TSS, thereby facilitating transcription (13).…”