Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association

Ng, Huck Hui; Feng, Qin; Wang, Hengbin; Erdjument‐Bromage, Hediye; Tempst, Paul; Zhang, Yi; Struhl, Kevin

doi:10.1101/gad.1001502

Cited by 507 publications

(484 citation statements)

References 56 publications

Supporting

Mentioning

454

Contrasting

Unclassified

Order By: Relevance

“…We examined mutants of SET2 (encoding an H3K36 histone methylase, 34), since it has been recently reported (35)(36)(37) that Set2p-dependent methylation recruits an Rpd3p-containing repressive complex (Rpd3C[S]). We also examined the effects of eliminating Dot1p, an H3K79 histone methyltransferase (38,39). H3K79 methylation is at low levels at yeast telomeres (40), but occurs at high levels at activelytranscribed genes (41).…”

Section: Introductionmentioning

confidence: 99%

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

et al. 2008

View full text Add to dashboard Cite

The rate of meiotic recombination in the yeast Saccharomyces cerevisiae varies widely in different regions of the genome with some genes having very high levels of recombination (hotspots). A variety of experiments done in yeast suggest that hotspots are a feature of chromatin structure rather than a feature of primary DNA sequence. We examined the effects of mutating a variety of enzymes that affect chromatin structure on the recombination activity of the well-characterized HIS4 hotspot including the Set2p and Dot1p histone methylases, the Hda1p and Rpd3p histone deacetylases, the Sin4p global transcription regulator, and a deletion of one of the two copies of the genes encoding histone H3-H4. Loss of Set2p or Rpd3p substantially elevated HIS4 hotspot activity, and loss of Hda1p had a smaller stimulatory effect; none of the other alterations had a significant effect. The increase of HIS4 hotspot activity in set2 and rpd3 strains is likely to be related to the recent finding that histone H3 methylation by Set2p directs deacetylation of histones by Rpd3p. IntroductionThe rate of meiotic recombination varies considerably at different positions in the yeast genome (1,2). This variation reflects differences in the frequency of local meiosis-specific doublestrand DNA breaks (DSBs), the recombination-initiating lesion (3,4) catalyzed by Spo11p and associated proteins (5). There are several lines of evidence that the frequency of DSBs is regulated by elements of chromatin structure rather than primary DNA sequence (2). First, recombination hotspots exhibit hypersensitivity to nucleases (6-10). Some loci (8,9) undergo meiosis-specific alterations in nuclease sensitivity prior to DSB formation, although no such changes are observed at other loci (6). Since all nuclease-hypersensitive regions are not meiotic Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain.Conflicts of interest None. NIH Public AccessAuthor Manuscript DNA Repair (Amst) (6,10), "open" chromatin appears necessary, but not sufficient, for meiotic recombination hotspot activity. Second, insertion of a nucleosome-excluding sequence into the yeast genome creates a recombination hotspot (11). Third, the activity of some hotspots requires the binding of transcription factors, but not high levels of transcription (2). This result has been interpreted as indicating that chromatin modifications associated with transcription factor binding stimulate both transcription and recombination. Finally, some mutants that affect chromatin modifications reduce the frequency of meiosis-specific DSBs. In the yeast S. pombe, mutatio...

show abstract

Section: Introductionmentioning

confidence: 99%

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

et al. 2008

View full text Add to dashboard Cite

show abstract

“…It has a tyrosine at the position comparable with Phe281 of DIM-5, and yet appears to be responsilnle for di-and tri-methylation of H3 Lys-4 in vivo [51,60]. It should be noted, however, that the published studies in 2002 did not reveal whether SET1 also produces mono-methyl-Lys-4, presumably because the mono-specific antibody was not yet available.…”

Section: A Tyrosine/phenylalanine Switch Controls Product Specificitymentioning

confidence: 99%

“…Histone H3 Lys-79 is methylated by Dot1p [60,[67][68][69], a protein originally identified as a disruptor of telomeric silencing in S. cerevisiae [70]. Methylation of H3 Lys-79 in S. cerevisiae is important for the proper localization of the SIR (silent information regulator) complex [60,69] and DNA damage signaling [71,72].…”

Section: Dot1p: Non-set Domain Hkmtmentioning

confidence: 99%

“…Methylation of H3 Lys-79 in S. cerevisiae is important for the proper localization of the SIR (silent information regulator) complex [60,69] and DNA damage signaling [71,72]. In human, mistargeting of hDOT1L to Hoxa9 (a leukemia-relevant gene) plays an important role in MLL (mixed lineage leukemia)-AF10-mediated leukemogenesish [73].…”

Section: Dot1p: Non-set Domain Hkmtmentioning

confidence: 99%

“…Dot1p has several unique biochemical properties. Yeast Dot1p and its human homolog Dot1L methylate only nucleosomal substrates, but not free histone H3 protein [60,[67][68][69]. A stretch of positively charged residues C-terminal to the human Dot1L core or N-terminal to the yeast Dot1p core (Figure 4a) were critical for nucleosome binding and therefore for enzymatic activity [76,77].…”

Section: Dot1p: Non-set Domain Hkmtmentioning

confidence: 99%

See 2 more Smart Citations

Structural dynamics of protein lysine methylation and demethylation

Cheng

Zhang

2007

Mutation Research/Fundamental and Molecular Mechanisms of Mutag

View full text Add to dashboard Cite

Lysine methylation plays a central role in the "histone code" that regulates chromatin structure, impacts transcription, and responds to DNA damage. A single lysine can be mono-, di-, trimethylated, or unmethylated, with different functional consequences for each of the four forms. This review describes structural aspects of methylation of histone lysine residues by two enzyme families with entirely different structural scaffolding (the SET proteins and Dot1p), and the protein motifs that recognize (decode) these methyl-lysine signals. We also discuss the recently discovered protein lysine de-methylating enzymes (LSD1 and JmjC domains). Keywordsprotein lysine methylation and demethylation; SET domain proteins; S-adenosyl-L-methionine (AdoMet)

show abstract

Transcriptional silencing

2015

The Dictionary of Genomics, Transcriptomics and Proteomics

View full text Add to dashboard Cite

Silent chromatin in budding yeast is characterized by the presence of a specialized chromatin modification complex consisting of silent information regulator (Sir) proteins, closely packed pairs of nucleosomes, and hypoacetylated and hypomethylated histones. How this specialized chromatin is established, maintained and inherited has been extensively studied. Less investigated are the determinants that constrain its linear spread along the chromatin fibre and the manner by which it represses gene transcription. Here we review the essential features of SIR-mediated heterochromatin, and discuss genomic and proteomic approaches for discerning the composition of its boundaries and for elucidating the mechanisms by which it silences transcription. Lu Gao is an orthopaedic surgeon. He is also a predoctoral student of Biochemistry and Molecular Biology, and is studying mechanisms of epigenetic gene silencing for his PhD degree. David S. Gross is a professor at the Louisiana State University Health Sciences Center. He is interested in mechanisms by which chromatin regulates gene expression. Current projects in his lab are focused on transcriptional silencing, heat shock gene regulation and p53 transcriptional regulatory mechanisms.

show abstract

Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association

Cited by 507 publications

References 56 publications

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

The histone methylase Set2p and the histone deacetylase Rpd3p repress meiotic recombination at the HIS4 meiotic recombination hotspot in Saccharomyces cerevisiae

Structural dynamics of protein lysine methylation and demethylation

Transcriptional silencing

Contact Info

Product

Resources

About