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

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.

NAD+-dependent deacetylation of H4 lysine 16 by class III HDACs

“…It is also found with the active transcription mark H3K4me3 in chromatin from yeast to humans (Millar et al, 2006;O'Neill et al, 2006). However, H4K16 acetylation antagonizes some other acetylated residues like H2BK18 and methylated residues like H3K79 (Kurdistani et al, 2004, Vaquero et al, 2004, H3K9 (Vaquero et al, 2004;O'Neill et al, 2006), H4K20me1 (Vaquero et al, 2004), H3K27 (Rougeulle et al, 2004), and probably H4 sumoylation and arginine methylation Nathan et al, 2006). Yet, there is some evidence that suggests the coexistence of monoacetyl K16 and H4K20me2,3 within the same H4 tail.…”

Regulation of chromatin by histone modifications

“…The modification is removed via the action of isopeptidases Sumoylation is a modification related to ubiquitylation [45], and involves the covalent attachment of small ubiquitin-like modifier molecules to histone lysines via the action of E1, E2 and E3 enzymes. Sumoylation has been detected on all four core histones and seems to function by antagonizing acetylation and ubiquitylation that might otherwise occur on the same lysine side chain [46,47]. Consequently, it has mainly been associated with repressive functions, but more work is clearly needed to elucidate the molecular mechanism(s) through which sumoylation exerts its effect on chromatin.…”

Epigenetic changes associated with oocyte aging

“…Except for methylation modification of DNA, there are diverse forms of modifications at the histone amino termini, including acetylation, phosphorylation, methylation, ADPribosylation, ubiquitination, sumoylation, biotinylation and proline isomerization [19][20][21][22][23][24][25]. It has been well documented that these histone modifications play important roles in cell cycle progression, DNA replication and repair, transcriptional activity and chromosome stability [26][27][28].…”