Abstract
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.
Highlights
Highly conserved residues and modifiable residues are likely to generate phenotypes[11]
In order to identify dynamic regions of nucleosome occupancy in the mutants, we divided the S. cerevisiae genome into 24,135 continuous 0.5-kb genomic segments and calculated the correlation coefficient of the nucleosome occupancy between the mutant and the wild-type strain for each segment
The 22 different histone mutations resulted in distinct nucleosome alterations (Fig. 1a and Table S3)
Summary
Highly conserved residues and modifiable residues are likely to generate phenotypes[11]. Histone mutations frequently disrupt transcription and alter chromatin organization at telomeres. Mutations of histones can alter the genome-wide nucleosome organization[7,12]. With respect to the underlying mechanism, histone mutations can affect the function of chromatin remodelling enzymes, altering nucleosome organization. Histone deletions and substitutions are known to affect nucleosomes[7,15,17], the genome-wide effects such as nucleosome alterations at specific genomic regions (such as the telomeres, both ends of a gene) and changes in the nucleosome array need to be explored, especially for mutations at modifiable amino acids of histones. The first nucleosomes upstream (− 1) and downstream (+ 1) of TSS (the − 1 and + 1 nucleosomes) are highly dynamic Expressed genes, such as ribosome genes and the genes involved in glycolysis, are sensitive to histone mutations.
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
