Limits...
Distal chromatin structure influences local nucleosome positions and gene expression.

Jansen A, van der Zande E, Meert W, Fink GR, Verstrepen KJ - Nucleic Acids Res. (2012)

Bottom Line: In addition, we show that changes in the nucleosome positions in the URA3 promoter strongly affect the promoter activity.Most interestingly, in addition to demonstrating the effect of the local DNA sequence, our study provides novel in vivo evidence that nucleosome positions are also affected by the position of neighboring nucleosomes.Nucleosome structure may therefore be an important selective force for conservation of gene order on a chromosome, because relocating a gene to another genomic position (where the positions of neighboring nucleosomes are different from the original locus) can have dramatic consequences for the gene's nucleosome structure and thus its expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Systems Biology, VIB, Bio-Incubator, Gaston Geenslaan 1, B-3001, Leuven, Belgium.

ABSTRACT
The positions of nucleosomes across the genome influence several cellular processes, including gene transcription. However, our understanding of the factors dictating where nucleosomes are located and how this affects gene regulation is still limited. Here, we perform an extensive in vivo study to investigate the influence of the neighboring chromatin structure on local nucleosome positioning and gene expression. Using truncated versions of the Saccharomyces cerevisiae URA3 gene, we show that nucleosome positions in the URA3 promoter are at least partly determined by the local DNA sequence, with so-called 'anti-nucleosomal elements' like poly(dA:dT) tracts being key determinants of nucleosome positions. In addition, we show that changes in the nucleosome positions in the URA3 promoter strongly affect the promoter activity. Most interestingly, in addition to demonstrating the effect of the local DNA sequence, our study provides novel in vivo evidence that nucleosome positions are also affected by the position of neighboring nucleosomes. Nucleosome structure may therefore be an important selective force for conservation of gene order on a chromosome, because relocating a gene to another genomic position (where the positions of neighboring nucleosomes are different from the original locus) can have dramatic consequences for the gene's nucleosome structure and thus its expression.

Show MeSH
Genomic context influences the positions of the −1 and +1 nucleosomes of a truncated URA3 promoter. The genomic context of each insertion site was quantified by measuring the position of the first nucleosome n upstream of each insertion site before insertion of the URA3 gene (Figure 2B) and %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. The positions of the −1 nucleosome (A), the positions of +1 nucleosome (B) and the distance between the −1 and +1 nucleosomes (C) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against the position of nucleosome n before insertion. The positions of the −1 nucleosome (D), the positions of +1 nucleosome (E) and the distance between the −1 and +1 nucleosomes (F) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. For each plot, the Pearson correlation coefficient was calculated.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC3351160&req=5

gkr1311-F6: Genomic context influences the positions of the −1 and +1 nucleosomes of a truncated URA3 promoter. The genomic context of each insertion site was quantified by measuring the position of the first nucleosome n upstream of each insertion site before insertion of the URA3 gene (Figure 2B) and %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. The positions of the −1 nucleosome (A), the positions of +1 nucleosome (B) and the distance between the −1 and +1 nucleosomes (C) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against the position of nucleosome n before insertion. The positions of the −1 nucleosome (D), the positions of +1 nucleosome (E) and the distance between the −1 and +1 nucleosomes (F) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. For each plot, the Pearson correlation coefficient was calculated.

Mentions: Finally, we examined whether the chromatin context of the insertion site determines the positions of the −1 and +1 nucleosomes in the lys2::URA3 reporter strains. Two parameters were used to study the effects of chromatin context. The first parameter is the position of nucleosome n, the nucleosome immediately upstream of each insertion site before insertion of the URA3 gene (Figure 2B). This nucleosome acts as the −1 nucleosome of the URA3 promoter after insertion. Our data show that there is a good correlation between the position of the -1 nucleosome after insertion and the position of nucleosome n before insertion (R = −0.74, P < 5 × 10−5) (Figure 6A). This result may suggest that the position of nucleosome n does not change upon insertion of URA3. However, when URA3 is inserted at or close to the center of nucleosome n, this nucleosome moves upstream, away from the URA3 promoter. On the other hand, when URA3 is inserted close to the nucleosome border or in a region devoid of nucleosomes, nucleosome n shifts downstream, towards the URA3 promoter.Figure 6.


Distal chromatin structure influences local nucleosome positions and gene expression.

Jansen A, van der Zande E, Meert W, Fink GR, Verstrepen KJ - Nucleic Acids Res. (2012)

Genomic context influences the positions of the −1 and +1 nucleosomes of a truncated URA3 promoter. The genomic context of each insertion site was quantified by measuring the position of the first nucleosome n upstream of each insertion site before insertion of the URA3 gene (Figure 2B) and %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. The positions of the −1 nucleosome (A), the positions of +1 nucleosome (B) and the distance between the −1 and +1 nucleosomes (C) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against the position of nucleosome n before insertion. The positions of the −1 nucleosome (D), the positions of +1 nucleosome (E) and the distance between the −1 and +1 nucleosomes (F) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. For each plot, the Pearson correlation coefficient was calculated.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3351160&req=5

gkr1311-F6: Genomic context influences the positions of the −1 and +1 nucleosomes of a truncated URA3 promoter. The genomic context of each insertion site was quantified by measuring the position of the first nucleosome n upstream of each insertion site before insertion of the URA3 gene (Figure 2B) and %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. The positions of the −1 nucleosome (A), the positions of +1 nucleosome (B) and the distance between the −1 and +1 nucleosomes (C) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against the position of nucleosome n before insertion. The positions of the −1 nucleosome (D), the positions of +1 nucleosome (E) and the distance between the −1 and +1 nucleosomes (F) of the URA3-163 promoter after insertion into various locations of the LYS2 gene are plotted against %AT content at the junction between the upstream LYS2 sequence and the URA3 promoter. For each plot, the Pearson correlation coefficient was calculated.
Mentions: Finally, we examined whether the chromatin context of the insertion site determines the positions of the −1 and +1 nucleosomes in the lys2::URA3 reporter strains. Two parameters were used to study the effects of chromatin context. The first parameter is the position of nucleosome n, the nucleosome immediately upstream of each insertion site before insertion of the URA3 gene (Figure 2B). This nucleosome acts as the −1 nucleosome of the URA3 promoter after insertion. Our data show that there is a good correlation between the position of the -1 nucleosome after insertion and the position of nucleosome n before insertion (R = −0.74, P < 5 × 10−5) (Figure 6A). This result may suggest that the position of nucleosome n does not change upon insertion of URA3. However, when URA3 is inserted at or close to the center of nucleosome n, this nucleosome moves upstream, away from the URA3 promoter. On the other hand, when URA3 is inserted close to the nucleosome border or in a region devoid of nucleosomes, nucleosome n shifts downstream, towards the URA3 promoter.Figure 6.

Bottom Line: In addition, we show that changes in the nucleosome positions in the URA3 promoter strongly affect the promoter activity.Most interestingly, in addition to demonstrating the effect of the local DNA sequence, our study provides novel in vivo evidence that nucleosome positions are also affected by the position of neighboring nucleosomes.Nucleosome structure may therefore be an important selective force for conservation of gene order on a chromosome, because relocating a gene to another genomic position (where the positions of neighboring nucleosomes are different from the original locus) can have dramatic consequences for the gene's nucleosome structure and thus its expression.

View Article: PubMed Central - PubMed

Affiliation: Laboratory for Systems Biology, VIB, Bio-Incubator, Gaston Geenslaan 1, B-3001, Leuven, Belgium.

ABSTRACT
The positions of nucleosomes across the genome influence several cellular processes, including gene transcription. However, our understanding of the factors dictating where nucleosomes are located and how this affects gene regulation is still limited. Here, we perform an extensive in vivo study to investigate the influence of the neighboring chromatin structure on local nucleosome positioning and gene expression. Using truncated versions of the Saccharomyces cerevisiae URA3 gene, we show that nucleosome positions in the URA3 promoter are at least partly determined by the local DNA sequence, with so-called 'anti-nucleosomal elements' like poly(dA:dT) tracts being key determinants of nucleosome positions. In addition, we show that changes in the nucleosome positions in the URA3 promoter strongly affect the promoter activity. Most interestingly, in addition to demonstrating the effect of the local DNA sequence, our study provides novel in vivo evidence that nucleosome positions are also affected by the position of neighboring nucleosomes. Nucleosome structure may therefore be an important selective force for conservation of gene order on a chromosome, because relocating a gene to another genomic position (where the positions of neighboring nucleosomes are different from the original locus) can have dramatic consequences for the gene's nucleosome structure and thus its expression.

Show MeSH