Nucleosome Stability Distinguishes Two Different Promoter Types at All Protein-Coding Genes in Yeast

Kubik, Slawomir; Bruzzone, Maria Jessica; Jacquet, Philippe; Falcone, Jean-Luc; Rougemont, Jacques; Shore, David

doi:10.1016/j.molcel.2015.10.002

Cited by 185 publications

(423 citation statements)

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“…Results from yeast (Weiner et al 2010;Xi et al 2011;Kubik et al 2015), plants (Vera et al 2014), mouse (Lombraña et al 2013;Deng et al 2015;Iwafuchi-Doi et al 2016;Mieczkowski et al 2016), worm (Ooi et al 2010), and fly (Henikoff et al 2009; have identified highly labile nucleosomes in 5 ′ and 3 ′ "nucleosome-free" regions. In yeast, Xi et al (2011) observed that fragile nucleosomes were associated with H2A.Z-containing promoter nucleosomes, believed to be involved in stress response (Li et al 2005;Zhang et al 2005).…”

Section: Mnase-resistant Nucleosomes Tend To Be In Gene Bodies and Comentioning

confidence: 99%

“…Studies in yeast, C. elegans, Drosophila, and maize have used salt profiling and different MNase concentrations to identify a positive correlation between promoter fragility and expression (Henikoff et al 2009;Ooi et al 2010;Vera et al 2014;Kubik et al 2015). However, Xi et al (2011) used the same approach and observed the opposite effect.…”

Section: Mnase-resistant Nucleosomes Tend To Be In Gene Bodies and Comentioning

confidence: 99%

“…Genome-wide adaptations of these methods have been used to identify nucleosome position and stability in vivo. Studies in yeast, Drosophila, plants, and mammals have used varying concentrations of the enzyme micrococcal nuclease (MNase) to identify nucleosomes with differential sensitivity to MNase digestion in vivo (Weiner et al 2010;Henikoff et al 2011;Xi et al 2011;Lombraña et al 2013;Vera et al 2014;Kubik et al 2015). Nucleosomes sensitive to low concentrations of MNase have been labeled as "fragile" and have been associated with TF binding sites (TFBSs) (Vera et al 2014), active origins of replication (Lombraña et al 2013), gene promoters (Xi et al 2011), and genomic sequences with high AT content .…”

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confidence: 99%

“…However, the functional implication of nucleosome fragility remains unclear. For example, one study reported fragile nucleosomes at the promoters of repressed stress-response genes during normal growth (Xi et al 2011), while another found fragile nucleosomes at the promoters of highly transcribed genes in yeast (Kubik et al 2015). We performed a time-course of MNase digestion in Caenorhabditis elegans mixed-stage embryos to study the relationship between fragility and gene activity in a developing multicellular organism.…”

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Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Jeffers

Lieb

2016

Genome Res.

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Nucleosomes have structural and regulatory functions in all eukaryotic DNA-templated processes. The position of nucleosomes on DNA and the stability of the underlying histone-DNA interactions affect the access of regulatory proteins to DNA. Both stability and position are regulated through DNA sequence, histone post-translational modifications, histone variants, chromatin remodelers, and transcription factors. Here, we explored the functional implications of nucleosome properties on gene expression and development in Caenorhabditis elegans embryos. We performed a time-course of micrococcal nuclease (MNase) digestion and measured the relative sensitivity or resistance of nucleosomes throughout the genome. Fragile nucleosomes were defined by nucleosomal DNA fragments that were recovered preferentially in early MNase-digestion time points. Nucleosome fragility was strongly and positively correlated with the AT content of the underlying DNA sequence. There was no correlation between promoter nucleosome fragility and the levels of histone modifications or histone variants. Genes with fragile nucleosomes in their promoters tended to be lowly expressed and expressed in a contextspecific way, operating in neuronal response, the immune system, and stress response. In addition to DNA-encoded nucleosome fragility, we also found fragile nucleosomes at locations where we expected to find destabilized nucleosomes, for example, at transcription factor binding sites where nucleosomes compete with DNA-binding factors. Our data suggest that in C. elegans promoters, nucleosome fragility is in large part DNA-encoded and that it poises genes for future context-specific activation in response to environmental stress and developmental cues.[Supplemental material is available for this article.]The fundamental unit of eukaryotic chromatin is the nucleosome, which consists of 147 bp of DNA wrapped around an octamer of histone proteins (Luger et al. 1997). Nucleosomes have important structural and regulatory functions in organizing the genome and restricting access of regulatory factors to the DNA sequence (Henikoff 2008). As such, the interactions between nucleosomes and DNA strongly influence the regulation of gene expression by determining DNA accessibility for transcription factors (TFs) and RNA polymerase. In addition to regulated nucleosome assembly and disassembly through the action of histone chaperones and chromatin remodelers, nucleosome stability is influenced by histone modifications, histone variants, DNA features encoded in cis, and competition with DNA-binding factors in trans . A complete picture of the mechanisms governing nucleosome stability is fundamental to understanding how gene expression is dynamically regulated.Nucleosome stability has been studied in vitro using sensitivity to enzymatic digestion or salt concentration (Bloom and Anderson 1978;Burton et al. 1978;Li et al. 1993;Polach and Widom 1995;Wu and Travers 2004;Jin and Felsenfeld 2007). Genome-wide adaptations of these methods have been used to identify nuc...

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Section: Mnase-resistant Nucleosomes Tend To Be In Gene Bodies and Comentioning

confidence: 99%

Section: Mnase-resistant Nucleosomes Tend To Be In Gene Bodies and Comentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

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Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Jeffers

Lieb

2016

Genome Res.

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“…GTFs are also connected to particularly fragile nucleosome promoter architectures (Xi et al, 2011), a connection recently examined (Kubik et al, 2015). Using this data, we computed the nucleosome landscape for the different gene classes (Methods).…”

Section: Resultsmentioning

confidence: 99%

Complex genetic and epigenetic regulation deviates gene expression from a unifying global transcriptional program

Chagoyen

Poyatos

2018

Preprint

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Environmental or genetic perturbations lead to gene expression changes. While most analyses of these changes emphasize the presence of qualitative differences on just a few genes, we now know that changes are widespread. This large-scale variation has been linked to the exclusive influence of a global transcriptional program determined by the new physiological state of the cell. However, given the sophistication of eukaryotic regulation, we expect to have a complex structure of deviations from the global program. Here, we examine the regulatory landscape that contributes to these deviations. Using data of Saccharomyces cerevisiae expression in different nutrient conditions, we first propose a five-component genome partition as a framework to understand expression variation. In this framework, we recognize invariant genes, whose regulation is dominated by the global program, specific genes, which substantially depart from it, and two additional classes that respond to intermediate regulatory schemes. Whereas the invariant class shows a considerable absence of specific regulation, the rest is enriched by regulation at the level of transcription factors (TFs) and epigenetic modulators. We nevertheless find markedly different strategies in how these classes deviate. On the one hand, there are TFs that act in an exclusive way between partition constituents, and on the other, the action of chromatin modifiers is significantly diverse. The balance between regulatory strategies ultimately modulates the action of the general transcription machinery, and therefore limits the possibility of establishing a single program of expression change at a genomic scale.All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.

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Establishing nucleosome architecture and stability at promoters: Roles of pioneer transcription factors and the RSC chromatin remodeler

2017

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Improvements in deep sequencing, together with methods to rapidly deplete essential transcription factors (TFs) and chromatin remodelers, have recently led to a more detailed picture of promoter nucleosome architecture in yeast and its relationship to transcriptional regulation. These studies revealed that ∼40% of all budding yeast protein-coding genes possess a unique promoter structure, where we propose that an unusually unstable nucleosome forms immediately upstream of the transcription start site (TSS). This "fragile" nucleosome (FN) promoter architecture relies on the combined action of the essential RSC (Remodels Structure of Chromatin) nucleosome remodeler and pioneer transcription factors (PTFs). FNs are associated with genes whose expression is high, coupled to cell growth, and characterized by low cell-to-cell variability (noise), suggesting that they may promote these features. Recent studies in metazoans suggest that the presence of dynamic nucleosomes upstream of the TSS at highly expressed genes may be conserved throughout evolution.

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Nucleosome Stability Distinguishes Two Different Promoter Types at All Protein-Coding Genes in Yeast

Cited by 185 publications

References 51 publications

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Nucleosome fragility is associated with future transcriptional response to developmental cues and stress inC. elegans

Complex genetic and epigenetic regulation deviates gene expression from a unifying global transcriptional program

Establishing nucleosome architecture and stability at promoters: Roles of pioneer transcription factors and the RSC chromatin remodeler

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