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Histone sumoylation is a negative regulator in Saccharomyces cerevisiae and shows dynamic interplay with positive-acting histone modifications. Genes Dev

Gene Expression and Regulation Program, The Wistar Institute, Philadelphia, Pennsylvania 19104, USA.
Genes & Development (Impact Factor: 12.64). 05/2006; 20(8):966-76. DOI: 10.1101/gad.1404206
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ABSTRACT Covalent histone post-translational modifications such as acetylation, methylation, phosphorylation, and ubiquitylation play pivotal roles in regulating many cellular processes, including transcription, response to DNA damage, and epigenetic control. Although positive-acting post-translational modifications have been studied in Saccharomyces cerevisiae, histone modifications that are associated with transcriptional repression have not been shown to occur in this yeast. Here, we provide evidence that histone sumoylation negatively regulates transcription in S. cerevisiae. We show that all four core histones are sumoylated and identify specific sites of sumoylation in histones H2A, H2B, and H4. We demonstrate that histone sumoylation sites are involved directly in transcriptional repression. Further, while histone sumoylation occurs at all loci tested throughout the genome, slightly higher levels occur proximal to telomeres. We observe a dynamic interplay between histone sumoylation and either acetylation or ubiquitylation, where sumoylation serves as a potential block to these activating modifications. These results indicate that sumoylation is the first negative histone modification to be identified in S. cerevisiae and further suggest that sumoylation may serve as a general dynamic mark to oppose transcription.

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Available from: Milos Dokmanovic, Aug 21, 2015
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    • "It is intriguing, nevertheless, how SUMO correlates with this effect. All core histones (H2A, H2B, H3 and H4) were found to be modified by SUMO in K residues that do not match the consensus, similar to what has been reported for H2A and H2B SUMOylation sites in yeast and humans (Nathan et al., 2006; Hendriks et al., 2014; Tammsalu et al., 2014). Since histones are very abundant proteins, they are expected to be easily detected when general SUMOylation patterns are analysed by Western blot; however, it is difficult to predict the apparent molecular weight of SUMOylated histones mainly because they can be SUMOylated at multiple K residues. "
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    Cellular Microbiology 06/2015; DOI:10.1111/cmi.12467 · 4.82 Impact Factor
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    • "However, histone sumoylation has been associated with inhibition of transcription (Nathan et al. 2006), whereas we found that Sumo has a positive function at the majority of its target genes (Table S3, Fig. 2B and Fig. S2A), making it unlikely that histones are Sumo targets at these genes. "
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    Genome Research 03/2015; 25(6). DOI:10.1101/gr.185793.114 · 13.85 Impact Factor
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    • "A second mechanism could rely on HDAC activation by SUMO because it was observed that lowered HDAC sumoylation may indirectly lead to higher histone acetylation (David et al. 2002; Cheng et al. 2004). In Saccharomyces cerevisiae, a higher level of H2B- SUMO was observed at telomeres than at more internal chromosomal sites, which may suggest the participation of histone sumoylation in telomeric silencing (Nathan et al. 2006). It is unclear whether sumoylation directly alters nucleosomal structure or packing and whether it promotes or inhibits interactions with non-histone proteins. "
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