Limits...
Nucleosome alterations caused by mutations at modifiable histone residues in Saccharomyces cerevisiae.

Liu H, Wang P, Liu L, Min Z, Luo K, Wan Y - Sci Rep (2015)

Bottom Line: We examined the effect of substituting modifiable residues of four core histones with the non-modifiable residue alanine on nucleosome dynamics.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.

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.

No MeSH data available.


Related in: MedlinePlus

The first nucleosomes upstream (−1) and downstream (+1) of a transcription start site (TSS) are dynamic in histone mutants.(a) Heat maps showing the log2 fold changes in nucleosome occupancy in the histone mutant strains relative to the wild-type strain for 5,419 genes. Data were aligned according to the TSS and grouped by transcription rate (rate < 1, 1 to <4, 4 to <16, 16 to <50, and ≥ 50; within each group, the genes were sorted by length). Data from mutants H2AK7A, H2BK123A, H3K36A, and H4K20A are shown. Nucleosome occupancy profiles are shown in Fig. S5a. (b) Differences in nucleosome occupancy around the TSS between mutant and wild-type strains. Each profile represents the average difference in occupancy between the mutant and the wild-type strain for 5,419 genes. The variation of dyad position and occupancy is shown in Fig. S4a. The significance of differences in occupancy is given in Fig. S4b. (c) Differences in nucleosome occupancy around the transcription termination sites between mutant and wild-type strains (analysis as for Fig. 2b; see also Fig. S4b). (d) Histone mutations disrupt the periodicity of the nucleosome distribution. The bar plot shows the intensities of Fourier spectra (see Fig. S6) of the distributions of nucleosomes with a periodicity of 157 bp, where the Fourier spectra highly peak, in the 22 mutants and the wild-type strains. The periodicity was calculated using the autocorrelation signal of the nucleosome occupancy profile of 16 chromosomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4620441&req=5

f2: The first nucleosomes upstream (−1) and downstream (+1) of a transcription start site (TSS) are dynamic in histone mutants.(a) Heat maps showing the log2 fold changes in nucleosome occupancy in the histone mutant strains relative to the wild-type strain for 5,419 genes. Data were aligned according to the TSS and grouped by transcription rate (rate < 1, 1 to <4, 4 to <16, 16 to <50, and ≥ 50; within each group, the genes were sorted by length). Data from mutants H2AK7A, H2BK123A, H3K36A, and H4K20A are shown. Nucleosome occupancy profiles are shown in Fig. S5a. (b) Differences in nucleosome occupancy around the TSS between mutant and wild-type strains. Each profile represents the average difference in occupancy between the mutant and the wild-type strain for 5,419 genes. The variation of dyad position and occupancy is shown in Fig. S4a. The significance of differences in occupancy is given in Fig. S4b. (c) Differences in nucleosome occupancy around the transcription termination sites between mutant and wild-type strains (analysis as for Fig. 2b; see also Fig. S4b). (d) Histone mutations disrupt the periodicity of the nucleosome distribution. The bar plot shows the intensities of Fourier spectra (see Fig. S6) of the distributions of nucleosomes with a periodicity of 157 bp, where the Fourier spectra highly peak, in the 22 mutants and the wild-type strains. The periodicity was calculated using the autocorrelation signal of the nucleosome occupancy profile of 16 chromosomes.

Mentions: The +1 and −1 nucleosomes tend to be dynamically regulated according to cell-associated changes1819. Here, we revealed that the +1 and −1 nucleosomes exhibited large occupancy changes in all 22 histone mutants (Fig. 2). We plotted the fold change (log2) of nucleosome occupancy of 5,419 genes between the mutant and the wild-type strains (Fig. 2a, only four mutants are shown because of limited space). The results indicate the obvious dynamics of nucleosome occupancy at gene promoters (Fig. 2a). We then plotted the average difference in nucleosome occupancy of the 5,419 genes between the mutant and wild-type strains (Fig. 2b). Consistent with Fig. 2a, b shows a high peak or a low valley at the +1 and −1 nucleosome positions. In mutants of histones H3 and H4, occupancy of the +1 and −1 nucleosomes was drastically increased (Fig. 2b and Fig. S4a [right]), whereas the occupancy of these two nucleosomes was decreased in mutants H2AK21A and H2AK7A (Fig. 2b). A large shift in dyad position was observed at the −1 nucleosome between the mutant and the wild-type strains (Fig. S4a [left]), suggesting a fuzzy positioning at the −1 nucleosome. In contrast, the +1 nucleosomal dyad position showed a small shift but a great occupancy alteration (Fig. S4a). In a further analysis (Fig. S4b [left]), a difference in occupancy was observed at the +1 nucleosome in mutants H2AS121A, H3S10A, and H4K20A (P < 10−20, t-test) and a difference at the +2 nucleosome was found in mutant H2BK16A. The nucleosome profiles and detailed dynamics of the +1 and −1 nucleosomes are shown in Fig. S5.


Nucleosome alterations caused by mutations at modifiable histone residues in Saccharomyces cerevisiae.

Liu H, Wang P, Liu L, Min Z, Luo K, Wan Y - Sci Rep (2015)

The first nucleosomes upstream (−1) and downstream (+1) of a transcription start site (TSS) are dynamic in histone mutants.(a) Heat maps showing the log2 fold changes in nucleosome occupancy in the histone mutant strains relative to the wild-type strain for 5,419 genes. Data were aligned according to the TSS and grouped by transcription rate (rate < 1, 1 to <4, 4 to <16, 16 to <50, and ≥ 50; within each group, the genes were sorted by length). Data from mutants H2AK7A, H2BK123A, H3K36A, and H4K20A are shown. Nucleosome occupancy profiles are shown in Fig. S5a. (b) Differences in nucleosome occupancy around the TSS between mutant and wild-type strains. Each profile represents the average difference in occupancy between the mutant and the wild-type strain for 5,419 genes. The variation of dyad position and occupancy is shown in Fig. S4a. The significance of differences in occupancy is given in Fig. S4b. (c) Differences in nucleosome occupancy around the transcription termination sites between mutant and wild-type strains (analysis as for Fig. 2b; see also Fig. S4b). (d) Histone mutations disrupt the periodicity of the nucleosome distribution. The bar plot shows the intensities of Fourier spectra (see Fig. S6) of the distributions of nucleosomes with a periodicity of 157 bp, where the Fourier spectra highly peak, in the 22 mutants and the wild-type strains. The periodicity was calculated using the autocorrelation signal of the nucleosome occupancy profile of 16 chromosomes.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4620441&req=5

f2: The first nucleosomes upstream (−1) and downstream (+1) of a transcription start site (TSS) are dynamic in histone mutants.(a) Heat maps showing the log2 fold changes in nucleosome occupancy in the histone mutant strains relative to the wild-type strain for 5,419 genes. Data were aligned according to the TSS and grouped by transcription rate (rate < 1, 1 to <4, 4 to <16, 16 to <50, and ≥ 50; within each group, the genes were sorted by length). Data from mutants H2AK7A, H2BK123A, H3K36A, and H4K20A are shown. Nucleosome occupancy profiles are shown in Fig. S5a. (b) Differences in nucleosome occupancy around the TSS between mutant and wild-type strains. Each profile represents the average difference in occupancy between the mutant and the wild-type strain for 5,419 genes. The variation of dyad position and occupancy is shown in Fig. S4a. The significance of differences in occupancy is given in Fig. S4b. (c) Differences in nucleosome occupancy around the transcription termination sites between mutant and wild-type strains (analysis as for Fig. 2b; see also Fig. S4b). (d) Histone mutations disrupt the periodicity of the nucleosome distribution. The bar plot shows the intensities of Fourier spectra (see Fig. S6) of the distributions of nucleosomes with a periodicity of 157 bp, where the Fourier spectra highly peak, in the 22 mutants and the wild-type strains. The periodicity was calculated using the autocorrelation signal of the nucleosome occupancy profile of 16 chromosomes.
Mentions: The +1 and −1 nucleosomes tend to be dynamically regulated according to cell-associated changes1819. Here, we revealed that the +1 and −1 nucleosomes exhibited large occupancy changes in all 22 histone mutants (Fig. 2). We plotted the fold change (log2) of nucleosome occupancy of 5,419 genes between the mutant and the wild-type strains (Fig. 2a, only four mutants are shown because of limited space). The results indicate the obvious dynamics of nucleosome occupancy at gene promoters (Fig. 2a). We then plotted the average difference in nucleosome occupancy of the 5,419 genes between the mutant and wild-type strains (Fig. 2b). Consistent with Fig. 2a, b shows a high peak or a low valley at the +1 and −1 nucleosome positions. In mutants of histones H3 and H4, occupancy of the +1 and −1 nucleosomes was drastically increased (Fig. 2b and Fig. S4a [right]), whereas the occupancy of these two nucleosomes was decreased in mutants H2AK21A and H2AK7A (Fig. 2b). A large shift in dyad position was observed at the −1 nucleosome between the mutant and the wild-type strains (Fig. S4a [left]), suggesting a fuzzy positioning at the −1 nucleosome. In contrast, the +1 nucleosomal dyad position showed a small shift but a great occupancy alteration (Fig. S4a). In a further analysis (Fig. S4b [left]), a difference in occupancy was observed at the +1 nucleosome in mutants H2AS121A, H3S10A, and H4K20A (P < 10−20, t-test) and a difference at the +2 nucleosome was found in mutant H2BK16A. The nucleosome profiles and detailed dynamics of the +1 and −1 nucleosomes are shown in Fig. S5.

Bottom Line: We examined the effect of substituting modifiable residues of four core histones with the non-modifiable residue alanine on nucleosome dynamics.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.

View Article: PubMed Central - PubMed

Affiliation: State Key Laboratory of Bioelectronics, Southeast University, Nanjing 210096, China.

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.

No MeSH data available.


Related in: MedlinePlus