Nucleosome alterations caused by mutations at modifiable histone residues in Saccharomyces cerevisiae.
Nucleosome organization exhibits dynamic properties depending on the cell state and environment. Histone proteins, fundamental components of nucleosomes, are subject to chemical modifications on particular residues. We examined the effect of substituting modifiable residues of four core histones with the non-modifiable residue alanine on nucleosome dynamics. We mapped the genome-wide nucleosomes in 22 histone mutants of Saccharomyces cerevisiae and compared the nucleosome alterations relative to the wild-type strain. Our results indicated that different types of histone mutation resulted in different phenotypes and a distinct reorganization of nucleosomes. Nucleosome occupancy was altered at telomeres, but not at centromeres. The first nucleosomes upstream (-1) and downstream (+1) of the transcription start site (TSS) were more dynamic than other nucleosomes. Mutations in histones affected the nucleosome array downstream of the TSS. Highly expressed genes, such as ribosome genes and genes involved in glycolysis, showed increased nucleosome occupancy in many types of histone mutant. In particular, the H3K56A mutant exhibited a high percentage of dynamic genomic regions, decreased nucleosome occupancy at telomeres, increased occupancy at the +1 and -1 nucleosomes, and a slow growth phenotype under stress conditions. Our findings provide insight into the influence of histone mutations on nucleosome dynamics.
State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.
Hongde
H
Liu
Institute of Life Sciences, Southeast University, Nanjing 210096, China.
Pingyan
P
Wang
State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.
Lingjie
L
Liu
Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Zhu
Z
Min
Department of Neurosurgery, Xinjiang Evidence-Based Medicine Research Institute, First Affiliated Hospital of Xinjiang Medical University, Urumqi 830054, China.
Kun
K
Luo
Institute of Life Sciences, Southeast University, Nanjing 210096, China.|Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Shanghai 201203, China.
Yakun
Y
Wan
D002503:Centromere; D042002:Chromatin Assembly and Disassembly; D015966:Gene Expression Regulation, Fungal; D016681:Genome, Fungal; D006657:Histones / Q000235:genetics*; D009154:Mutation; D009707:Nucleosomes / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000235:genetics / Q000378:metabolism*; D029701:Saccharomyces cerevisiae Proteins / Q000235:genetics; D016615:Telomere; D014157:Transcription Factors
D006657:Histones; D009707:Nucleosomes; D029701:Saccharomyces cerevisiae Proteins; D014157:Transcription Factors