PMID:29066473

Citation	Jaiswal, D, Jezek, M, Quijote, J, Lum, J, Choi, G, Kulkarni, R, Park, D and Green, EM (2017) Repression of Middle Sporulation Genes in by the Sum1-Rfm1-Hst1 Complex Is Maintained by Set1 and H3K4 Methylation. G3 (Bethesda) 7:3971-3982
Abstract	The conserved yeast histone methyltransferase Set1 targets H3 lysine 4 (H3K4) for mono, di, and trimethylation and is linked to active transcription due to the euchromatic distribution of these methyl marks and the recruitment of Set1 during transcription. However, loss of Set1 results in increased expression of multiple classes of genes, including genes adjacent to telomeres and middle sporulation genes, which are repressed under normal growth conditions because they function in meiotic progression and spore formation. The mechanisms underlying Set1-mediated gene repression are varied, and still unclear in some cases, although repression has been linked to both direct and indirect action of Set1, associated with noncoding transcription, and is often dependent on the H3K4me2 mark. We show that Set1, and particularly the H3K4me2 mark, are implicated in repression of a subset of middle sporulation genes during vegetative growth. In the absence of Set1, there is loss of the DNA-binding transcriptional regulator Sum1 and the associated histone deacetylase Hst1 from chromatin in a locus-specific manner. This is linked to increased H4K5ac at these loci and aberrant middle gene expression. These data indicate that, in addition to DNA sequence, histone modification status also contributes to proper localization of Sum1 Our results also show that the role for Set1 in middle gene expression control diverges as cells receive signals to undergo meiosis. Overall, this work dissects an unexplored role for Set1 in gene-specific repression, and provides important insights into a new mechanism associated with the control of gene expression linked to meiotic differentiation.
Links	PubMed PMC5714494 Online version:10.1534/g3.117.300150
Keywords	Chromatin/genetics; DNA Methylation/genetics; DNA-Binding Proteins/genetics; Gene Expression Regulation, Fungal; Histone-Lysine N-Methyltransferase/genetics; Meiosis/genetics; Multiprotein Complexes/genetics; Nuclear Proteins/genetics; Repressor Proteins/genetics; Saccharomyces cerevisiae/genetics; Saccharomyces cerevisiae Proteins/genetics; Sirtuin 2/genetics; Spores, Fungal/genetics
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
YEAST:SET1		GO:0010629: negative regulation of gene expression	ECO:0000315:		P		Fig 1. Shows that in S. cerevisiae, the set1 gene is required for repressing the expression of other S. cerevisiae middle class sporulation genes during vegetative growth.	complete CACAO 13411
YEAST:SET1		GO:0090241: negative regulation of histone H4 acetylation	ECO:0000315:		P		Fig. 5 shows that in S. cerevisiae lacking the set1 gene, H3K5 acetylation increases at middle sporulation loci.	complete CACAO 13413

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