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Multifaceted Genome Control by Set1 Dependent and Independent of H3K4 Methylation and the Set1C/COMPASS Complex


Methylation of histone H3 at lysine 4 (H3K4me) is a well-documented mark associated with euchromatin. In this study, we investigate the contributions of the histone methyltransferase Set1 (KMT2) and its associated Set1C/COMPASS complex in the fission yeast Schizosaccharomyces pombe to histone H3 lysine 4 methylation (H3K4me), transcriptional repression, and genome organization. We show that Set1 exhibits multiple modes of transcriptional repression at different types of repetitive elements, requiring distinct domains of Set1 and other Set1C subunits. Despite high conservation of subunits between the S. pombe and S. cerevisiae Set1C complexes, there are considerable differences in contributions to H3K4me by several individual subunits. Furthermore, unlike a recent report in S. cerevisiae, the abundance of Set1 proteins in S. pombe is generally not coupled to either the status of H3K4 methylation or H2B ubiquitination, further highlighting critical differences in Set1 regulation between the two yeast species. We describe a role for the Set1C complex in the nuclear organization of dispersed retrotransposons into Tf bodies. Set1C maintains Tf body integrity by employing H3K4me to antagonize the activities of the H3K4 acetyltransferase Mst1. Collectively, our findings dramatically expand the regulatory landscape controlled by the Set1C complex, an important and highly conserved chromatin-modifying complex with diverse roles in genome control and development.


Vyšlo v časopise: Multifaceted Genome Control by Set1 Dependent and Independent of H3K4 Methylation and the Set1C/COMPASS Complex. PLoS Genet 10(10): e32767. doi:10.1371/journal.pgen.1004740
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1004740

Souhrn

Methylation of histone H3 at lysine 4 (H3K4me) is a well-documented mark associated with euchromatin. In this study, we investigate the contributions of the histone methyltransferase Set1 (KMT2) and its associated Set1C/COMPASS complex in the fission yeast Schizosaccharomyces pombe to histone H3 lysine 4 methylation (H3K4me), transcriptional repression, and genome organization. We show that Set1 exhibits multiple modes of transcriptional repression at different types of repetitive elements, requiring distinct domains of Set1 and other Set1C subunits. Despite high conservation of subunits between the S. pombe and S. cerevisiae Set1C complexes, there are considerable differences in contributions to H3K4me by several individual subunits. Furthermore, unlike a recent report in S. cerevisiae, the abundance of Set1 proteins in S. pombe is generally not coupled to either the status of H3K4 methylation or H2B ubiquitination, further highlighting critical differences in Set1 regulation between the two yeast species. We describe a role for the Set1C complex in the nuclear organization of dispersed retrotransposons into Tf bodies. Set1C maintains Tf body integrity by employing H3K4me to antagonize the activities of the H3K4 acetyltransferase Mst1. Collectively, our findings dramatically expand the regulatory landscape controlled by the Set1C complex, an important and highly conserved chromatin-modifying complex with diverse roles in genome control and development.


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