Review
Choose Your Own Adventure: The Role of Histone Modifications in Yeast Cell Fate

https://doi.org/10.1016/j.jmb.2016.10.018Get rights and content

Highlights

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    Diverse histone modifications in Saccharomyces cerevisiae regulate cell fate decisions.

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    Histone-modifying enzymes are targeted by intrinsic and extrinsic signaling cues to regulate transcription and chromatin reorganization.

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    Histone modifications play critical roles in genomic reprogramming during meiotic sporulation, filamentous growth, and programmed cell death.

Abstract

When yeast cells are challenged by a fluctuating environment, signaling networks activate differentiation programs that promote their individual or collective survival. These programs include the initiation of meiotic sporulation, the formation of filamentous growth structures, and the activation of programmed cell death pathways. The establishment and maintenance of these distinct cell fates are driven by massive gene expression programs that promote the necessary changes in morphology and physiology. While these genomic reprogramming events depend on a specialized network of transcription factors, a diverse set of chromatin regulators, including histone-modifying enzymes, chromatin remodelers, and histone variants, also play essential roles. Here, we review the broad functions of histone modifications in initiating cell fate transitions, with particular focus on their contribution to the control of expression of key genes required for the differentiation programs and chromatin reorganization that accompanies these cell fates.

Section snippets

Histone Modifications of S. cerevisiae

The packaging of DNA into nucleosomes provides the structural foundation for genomic reprogramming events that underlie cell fate transitions. Nucleosomes are composed of the four core histones H3, H4, H2A, and H2B and may also have one of the two variant histones in budding yeast, Htz1 (H2A.Z), which marks heterochromatin–euchromatin boundaries and poised promoters [8], [9], or the centromere-specific H3 variant Cse4 (CENP-A) [10]. The role of individual nucleosomes in defining transcriptional

Nutrient-Responsive Signaling and Chromatin States

Changes to nutrient availability trigger multiple responses that promote the survival of yeast cells under fluctuating environmental conditions (Fig. 1). For example, nitrogen depletion, the absence of glucose and the presence of a nonfermentable carbon source, such as acetate, stimulates entry into sporulation [5], [32], a specialized cell fate in which MATa/α diploid cells undergo a meiotic division to produce haploid progeny (spores), which are packaged into a protective ascus. Sporulation

Chromatin Dynamics during PCD

PCD in metazoans has key developmental roles, such as promoting proper tissue architecture and the destruction of damaged cells, and aberrant regulation of PCD pathways is implicated in diseases including cancer and neurodegenerative disorders [7], [87]. Based on the lack of some cell death machinery, it was not clear that S. cerevisiae exhibited PCD until apoptosis-related phenotypes were observed in a CDC48 mutant. Observed phenotypes included DNA fragmentation, chromatin compaction,

Concluding Remarks

We have reviewed a number of significant advances in our understanding of chromatin modifications critical to yeast cell fates. In the representative cases cited here, key themes emerge and areas for further exploration are highlighted. First, while chromatin-modifying enzymes such as Rpd3, Gcn5, Set1, and Set2 have broad functions throughout the genome, they also have critical context-dependent roles responding to specific cues and acting within distinct genomic regions to advance cell fate

Acknowledgments

The authors acknowledge the members of the Green lab for fruitful discussions and comments on the manuscript. This work was supported in part by NIH R03AG052018 and a UMBC START award to E.M.G.

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