Journal article
Novel Functional Residues in the Core Domain of Histone H2B Regulate Yeast Gene Expression and Silencing and Affect the Response to DNA Damage
Molecular and cellular biology, Vol.30(14), pp.3503-3518
07/15/2010
Handle:
https://hdl.handle.net/2376/101356
PMCID: PMC2897548
PMID: 20479120
Abstract
ABSTRACT Previous studies have identified novel modifications in the core fold domain of histone H2B, but relatively little is known about the function of these putative histone modification sites. We have mutated core modifiable residues that are conserved in Saccharomyces cerevisiae histone H2B and characterized the effects of the mutants on yeast silencing, gene expression, and the DNA damage response. We identified three histone H2B core modifiable residues as functionally important. We find that mutating H2B K49 in yeast confers a UV sensitivity phenotype, and we confirm that the homologous residue in human histone H2B is acetylated and methylated in human cells. Our results also indicate that mutating H2B K111 impairs the response to methyl methanesulfonate (MMS)-induced DNA lesions and disrupts telomeric silencing and Sir4 binding. In contrast, mutating H2B R102 enhances silencing at yeast telomeres and the HML silent mating loci and increases Sir4 binding to these regions. The H2B R102A mutant also represses the expression of endogenous genes adjacent to yeast telomeres, which is likely due to the ectopic spreading of the Sir complex in this mutant strain. We propose a structural model by which H2B R102 and K111 regulate the binding of the Sir complex to the nucleosome.
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Details
- Title
- Novel Functional Residues in the Core Domain of Histone H2B Regulate Yeast Gene Expression and Silencing and Affect the Response to DNA Damage
- Creators
- McKenna N. M Kyriss - School of Molecular BiosciencesYi Jin - Molecular Plant SciencesIsaura J Gallegos - School of Molecular BiosciencesJames A Sanford - School of Molecular BiosciencesJohn J Wyrick - School of Molecular Biosciences, Molecular Plant Sciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164-4660
- Publication Details
- Molecular and cellular biology, Vol.30(14), pp.3503-3518
- Academic Unit
- Molecular Biosciences, School of
- Identifiers
- 99900546676801842
- Language
- English
- Resource Type
- Journal article