Evidence map›Paper›PMID 18391024›Full record

ArticleMolecular and cellular biology2008

Synthetic lethal screens identify gene silencing processes in yeast and implicate the acetylated amino terminus of Sir3 in recognition of the nucleosome core.

Tibor van Welsem, Floor Frederiks, Kitty F Verzijlbergen, Alex W Faber, Zara W Nelson, David A Egan, Daniel E Gottschling, Fred van Leeuwen

Abstract read
In one paragraph

Article in Molecular and cellular biology, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 41 papers.

0numbers the graph read from it
0cells of the map it votes in
41citing papers in PubMed
3.0field-weighted citation impact, top 8% of its field
1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

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3 · Its place in the literature

Who cites it

41 citing papers in PubMed, 66 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

8 authors at 3 institutions in 3 countries.

Tibor van WelsemThe Netherlands Cancer Institute, Division of Cellular Biochemistry, Plesmanlaan 121, 1066CX Amsterdam, The Netherlands.
Floor Frederiks
Kitty F Verzijlbergen
Alex W Faber
Zara W Nelson
David A Egan
Daniel E Gottschling
Fred van Leeuwen
Cape Town HVTN Immunology Laboratory / Hutchinson Centre Research Institute of South Africa · ZAOncode Institute · NLThe Netherlands Cancer Institute · NL

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dot1 methylates histone H3 lysine 79 (H3K79) on the nucleosome core and is involved in Sir protein-mediated silencing. Previous studies suggested that H3K79 methylation within euchromatin prevents nonspecific binding of the Sir proteins, which in turn facilitates binding of the Sir proteins in unmethylated silent chromatin. However, the mechanism by which the Sir protein binding is influenced by this modification is unclear. We performed genome-wide synthetic genetic array (SGA) analysis and identified interactions of DOT1 with SIR1 and POL32. The synthetic growth defects found by SGA analysis were attributed to the loss of mating type identity caused by a synthetic silencing defect. By using epistasis analysis, DOT1, SIR1, and POL32 could be placed in different pathways of silencing. Dot1 shared its silencing phenotypes with the NatA N-terminal acetyltransferase complex and the conserved N-terminal bromo adjacent homology (BAH) domain of Sir3 (a substrate of NatA). We classified all of these as affecting a common silencing process, and we show that mutations in this process lead to nonspecific binding of Sir3 to chromatin. Our results suggest that the BAH domain of Sir3 binds to histone H3K79 and that acetylation of the BAH domain is required for the binding specificity of Sir3 for nucleosomes unmethylated at H3K79.

Indexed as

Gene Expression Regulation, FungalGene SilencingGenes, LethalAcetylationChromatinDNA-Directed DNA PolymeraseHistone-Lysine N-MethyltransferaseHistonesMethylationNuclear ProteinsNucleosomesProtein Structure, TertiarySaccharomyces cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeChromatinDNA-Directed DNA PolymeraseDot1 protein, S cerevisiaeHistone-Lysine N-MethyltransferaseHistonesNuclear ProteinsNucleosomesPol32 protein, S cerevisiaeSaccharomyces cerevisiae ProteinsSilent Information Regulator Proteins, Saccharomyces cerevisiaeSIR1 protein, S cerevisiaeSIR3 protein, S cerevisiae

Identifiers

PMID18391024
PMCPMC2423298
OpenAlexW2074087246

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.