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Polycomb Repressive Complex 2 (PRC2) catalyzes the mono-, di-, and trimethylation of histone protein H3 on lysine 27 (H3K27), which is strongly associated with transcriptionally silent chromatin. The functional core of PRC2 is highly conserved in animals and consists of four subunits. One of these, SUZ12, has not been identified in the genetic model Caenorhabditis elegans , whereas C. elegans PRC2 contains the clade-specific MES-3 protein. Through unbiased sensitive sequence similarity searches complemented by high-quality structure predictions of monomers and multimers, we here demonstrate that MES-3 is a highly divergent ortholog of SUZ12. MES-3 shares protein folds and conserved residues of key domains with SUZ12 and is predicted to interact with core PRC2 members similar to SUZ12 in human PRC2. Thus, in agreement with previous genetic and biochemical studies, we provide evidence that C. elegans contains a diverged yet evolutionary conserved core PRC2, like other animals., Competing Interests: The authors declare no competing interests., (© 2022 The Author(s).)

The tremendous diversity in eukaryotic life forms can ultimately be traced back to evolutionary modifications at the level of molecular networks. Deep understanding of these modifications will not only explain cellular diversity, but will also uncover different ways to execute similar processes and expose the evolutionary 'rules' that shape the molecular networks. Here, we review the evolutionary dynamics of the spindle assembly checkpoint (SAC), a signaling network that guards fidelity of chromosome segregation. We illustrate how the interpretation of divergent SAC systems in eukaryotic species is facilitated by combining detailed molecular knowledge of the SAC and extensive comparative genome analyses. Ultimately, expanding this to other core cellular systems and experimentally interrogating such systems in organisms from all major lineages may start outlining the routes to and eventual manifestation of the cellular diversity of eukaryotic life., (Copyright © 2020 Elsevier Inc. All rights reserved.)

Histone proteins compact and stabilize the genomes of Eukarya and Archaea. By forming nucleosome(-like) structures they restrict access of DNA-binding transcription regulators to cis-regulatory DNA elements. Dynamic competition between histones and transcription factors is facilitated by different classes of proteins including ATP-dependent remodeling enzymes that control assembly, access, and editing of chromatin. Here, we summarize the knowledge on dynamics underlying transcriptional regulation across the domains of life with a focus on ATP-dependent enzymes in chromatin structure or in TATA-binding protein activity. These insights suggest directions for future studies on the evolution of transcription regulation and chromatin dynamics., (Copyright © 2015 Elsevier Inc. All rights reserved.)

To understand regulatory systems, it would be useful to uniformly determine how different components contribute to the expression of all other genes. We therefore monitored mRNA expression genome-wide, for individual deletions of one-quarter of yeast genes, focusing on (putative) regulators. The resulting genetic perturbation signatures reflect many different properties. These include the architecture of protein complexes and pathways, identification of expression changes compatible with viability, and the varying responsiveness to genetic perturbation. The data are assembled into a genetic perturbation network that shows different connectivities for different classes of regulators. Four feed-forward loop (FFL) types are overrepresented, including incoherent type 2 FFLs that likely represent feedback. Systematic transcription factor classification shows a surprisingly high abundance of gene-specific repressors, suggesting that yeast chromatin is not as generally restrictive to transcription as is often assumed. The data set is useful for studying individual genes and for discovering properties of an entire regulatory system., (Copyright © 2014 Elsevier Inc. All rights reserved.)

The mitotic checkpoint evolved to prevent cell division when chromosomes have not established connections with the chromosome segregation machinery. Many of the fundamental molecular principles that underlie the checkpoint, its spatiotemporal activation, and its timely inactivation have been uncovered. Most of these are conserved in eukaryotes, but important differences between species exist. Here we review current concepts of mitotic checkpoint activation and silencing. Guided by studies in model organisms and our phylogenomics analysis of checkpoint constituents and their functional domains and motifs, we highlight ancient and taxa-specific aspects of the core checkpoint modules in the context of mitotic checkpoint function., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Chromosomal stability is safeguarded by a mitotic checkpoint, of which BUB1 and Mad3/BUBR1 are core components. These paralogs have similar, but not identical, domain organization. We show that Mad3/BUBR1 and BUB1 paralogous pairs arose by nine independent gene duplications throughout evolution, followed by parallel subfunctionalization in which preservation of the ancestral, amino-terminal KEN box or kinase domain was mutually exclusive. In one exception, vertebrate BUBR1-defined by the KEN box-preserved the kinase domain but allowed nonconserved degeneration of catalytic motifs. Although BUBR1 evolved to a typical pseudokinase in some vertebrates, it retained the catalytic triad in humans. However, we show that putative catalysis by human BUBR1 is dispensable for error-free chromosome segregation. Instead, residues that interact with ATP in conventional kinases are essential for conformational stability in BUBR1. We propose that parallel evolution of BUBR1 orthologs rendered its kinase function dispensable in vertebrates, producing an unusual, triad-containing pseudokinase., (Copyright © 2012 Elsevier Inc. All rights reserved.)

The pattern of plant organ initiation at the shoot apical meristem (SAM), termed phyllotaxis, displays regularities that have long intrigued botanists and mathematicians alike. In the SAM, the central zone (CZ) contains a population of stem cells that replenish the surrounding peripheral zone (PZ), where organs are generated in regular patterns. These patterns differ between species and may change in response to developmental or environmental cues [1]. Expression analysis of auxin efflux facilitators of the PIN-FORMED (PIN) family combined with modeling of auxin transport has indicated that organ initiation is associated with intracellular polarization of PIN proteins and auxin accumulation [2-10]. However, regulators that modulate PIN activity to determine phyllotactic patterns have hitherto been unknown. Here we reveal that three redundantly acting PLETHORA (PLT)-like AP2 domain transcription factors control shoot organ positioning in the model plant Arabidopsis thaliana. Loss of PLT3, PLT5, and PLT7 function leads to nonrandom, metastable changes in phyllotaxis. Phyllotactic changes in plt3plt5plt7 mutants are largely attributable to misregulation of PIN1 and can be recapitulated by reducing PIN1 dosage, revealing that PLT proteins are key regulators of PIN1 activity in control of phyllotaxis., (Copyright © 2011 Elsevier Ltd. All rights reserved.)

To understand relationships between phosphorylation-based signaling pathways, we analyzed 150 deletion mutants of protein kinases and phosphatases in S. cerevisiae using DNA microarrays. Downstream changes in gene expression were treated as a phenotypic readout. Double mutants with synthetic genetic interactions were included to investigate genetic buffering relationships such as redundancy. Three types of genetic buffering relationships are identified: mixed epistasis, complete redundancy, and quantitative redundancy. In mixed epistasis, the most common buffering relationship, different gene sets respond in different epistatic ways. Mixed epistasis arises from pairs of regulators that have only partial overlap in function and that are coupled by additional regulatory links such as repression of one by the other. Such regulatory modules confer the ability to control different combinations of processes depending on condition or context. These properties likely contribute to the evolutionary maintenance of paralogs and indicate a way in which signaling pathways connect for multiprocess control., (Copyright © 2010 Elsevier Inc. All rights reserved.)