University of Massachusetts Medical School Faculty Publications

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Department of Biochemistry and Molecular Pharmacology

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Article Preprint


Amino Acids, Peptides, and Proteins | Fungi | Genetic Phenomena | Genomics


The packaging of eukaryotic genomes into nucleosomes plays critical roles in all DNA-templated processes, and chromatin structure has been implicated as a key factor in the evolution of gene regulatory programs. While the functions of many histone modifications appear to be highly conserved throughout evolution, some well-studied modifications such as H3K9 and H3K27 methylation are not found in major model organisms such as Saccharomyces cerevisiae, while other modifications gain/lose regulatory functions during evolution. To study such a transition we focused on H3K9 methylation, a heterochromatin mark found in metazoans and in the fission yeast S. pombe, but which has been lost in the lineage leading to the model budding yeast S. cerevisiae. We show that this mark is present in the relatively understudied yeast Kluyveromyces lactis, a Hemiascomycete that diverged from S. cerevisiae prior to the whole-genome duplication event that played a key role in the evolution of a primarily fermentative lifestyle. We mapped genome-wide patterns of H3K9 methylation as well as several conserved modifications. We find that well-studied modifications such as H3K4me3, H3K36me3, and H3S10ph exhibit generally conserved localization patterns. Interestingly, we show H3K9 methylation in K. lactis primarily occurs over highly-transcribed regions, including both Pol2 and Pol3 transcription units. We identified the H3K9 methylase as the ortholog of Set6, whose function in S. cerevisiae is obscure. Functionally, we show that deletion of KlSet6 does not affect highly H3K9me3-marked genes, providing another example of a major disconnect between histone mark localization and function. Together, these results shed light on surprising plasticity in the function of a widespread chromatin mark.


genomics, histone modifications, evolution, Kluyveromyces lactis, KlSet6, H3K4me3, chromatin

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bioRxiv 039776; doi: Link to preprint on bioRxiv service.

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