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Comparative Genomics Reveals Chd1 as a Determinant of Nucleosome Spacing in Vivo.

Hughes AL, Rando OJ - G3 (Bethesda) (2015)

Bottom Line: In contrast, the K. lactis gene encoding the ATP-dependent remodeler Chd1 was found to direct longer internucleosomal spacing in S. cerevisiae, establishing that this remodeler is partially responsible for the relatively long internucleosomal spacing observed in K. lactis.By analyzing several chimeric proteins, we find that sequence differences that contribute to the spacing activity of this remodeler are dispersed throughout the coding sequence, but that the strongest spacing effect is linked to the understudied N-terminal end of Chd1.Taken together, our data find a role for sequence evolution of a chromatin remodeler in establishing quantitative aspects of the chromatin landscape in a species-specific manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.

No MeSH data available.


Related in: MedlinePlus

The K. lactis CHD1 ortholog can direct longer average linkers in S. cerevisiae. (A) Nucleosome mapping for chd1Δ and CHD1 swap strains, as in Figure 1. (B) Quantitation of the shift in average nucleosome position for CHD1 swap strains. Nucleosome positions were called as in Weiner et al. (2010), and the average distance between nucleosomes in the K. lactis swap strain and the same nucleosomes in the strain with S. cerevisiae CHD1 is plotted for nucleosome positions −1 to +7. (C) Distance of each coding region nucleosome from the +1 nucleosome, for the S. cer and K. lac CHD1-containing strains, with corresponding p-values (paired, two-tailed t-test) shown in parentheses at the bottom.
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fig2: The K. lactis CHD1 ortholog can direct longer average linkers in S. cerevisiae. (A) Nucleosome mapping for chd1Δ and CHD1 swap strains, as in Figure 1. (B) Quantitation of the shift in average nucleosome position for CHD1 swap strains. Nucleosome positions were called as in Weiner et al. (2010), and the average distance between nucleosomes in the K. lactis swap strain and the same nucleosomes in the strain with S. cerevisiae CHD1 is plotted for nucleosome positions −1 to +7. (C) Distance of each coding region nucleosome from the +1 nucleosome, for the S. cer and K. lac CHD1-containing strains, with corresponding p-values (paired, two-tailed t-test) shown in parentheses at the bottom.

Mentions: In contrast, deletion of CHD1 alone dramatically alters the global chromatin in S. cerevisiae, particularly for nucleosomes over the middle and 3′ ends of coding regions, consistent with published reports (Gkikopoulos et al. 2011) (Figure 2A, Figure S1). Interestingly, complementation of this deletion with K. lactis CHD1 causes an increase in internucleosome spacing at the 3′ end of genes. This was observed in multiple biological replicates, and in strains where the K. lactis gene was either carried on a plasmid or integrated into the S. cerevisiae genome (Figure S2). By calling nucleosome peaks and determining the distance between adjacent nucleosomes, we see that nucleosomes throughout coding regions are spaced farther apart in the presence of K. lactis Chd1, although this effect is somewhat stronger for nucleosomes within the gene body than for 5′ nucleosomes (Figures 2, B and C, Figure S3). Although the nucleosome repeat length increases by ∼1.5 bp in the presence of K. lactis Chd1 at the 5′ end, K. lactis Chd1 expands the average internucleosome spacing by 3 bp subsequent to the +3 nucleosome (Figures 2, B and C, Figure S2, Figure S3). Chd1 thus appears to be involved in the measurement of internucleosome distances, and evolutionary divergence between the S. cerevisiae and K. lactis copies results in altered measurement of linker length (see Discussion). It is important to note that other factors must play a role in establishing linker length, because the increase in nucleosome spacing seen with the introduction of K. lactis Chd1 does not fully account for the ∼15 bp longer average linkers seen in the K. lactis genome.


Comparative Genomics Reveals Chd1 as a Determinant of Nucleosome Spacing in Vivo.

Hughes AL, Rando OJ - G3 (Bethesda) (2015)

The K. lactis CHD1 ortholog can direct longer average linkers in S. cerevisiae. (A) Nucleosome mapping for chd1Δ and CHD1 swap strains, as in Figure 1. (B) Quantitation of the shift in average nucleosome position for CHD1 swap strains. Nucleosome positions were called as in Weiner et al. (2010), and the average distance between nucleosomes in the K. lactis swap strain and the same nucleosomes in the strain with S. cerevisiae CHD1 is plotted for nucleosome positions −1 to +7. (C) Distance of each coding region nucleosome from the +1 nucleosome, for the S. cer and K. lac CHD1-containing strains, with corresponding p-values (paired, two-tailed t-test) shown in parentheses at the bottom.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4555225&req=5

fig2: The K. lactis CHD1 ortholog can direct longer average linkers in S. cerevisiae. (A) Nucleosome mapping for chd1Δ and CHD1 swap strains, as in Figure 1. (B) Quantitation of the shift in average nucleosome position for CHD1 swap strains. Nucleosome positions were called as in Weiner et al. (2010), and the average distance between nucleosomes in the K. lactis swap strain and the same nucleosomes in the strain with S. cerevisiae CHD1 is plotted for nucleosome positions −1 to +7. (C) Distance of each coding region nucleosome from the +1 nucleosome, for the S. cer and K. lac CHD1-containing strains, with corresponding p-values (paired, two-tailed t-test) shown in parentheses at the bottom.
Mentions: In contrast, deletion of CHD1 alone dramatically alters the global chromatin in S. cerevisiae, particularly for nucleosomes over the middle and 3′ ends of coding regions, consistent with published reports (Gkikopoulos et al. 2011) (Figure 2A, Figure S1). Interestingly, complementation of this deletion with K. lactis CHD1 causes an increase in internucleosome spacing at the 3′ end of genes. This was observed in multiple biological replicates, and in strains where the K. lactis gene was either carried on a plasmid or integrated into the S. cerevisiae genome (Figure S2). By calling nucleosome peaks and determining the distance between adjacent nucleosomes, we see that nucleosomes throughout coding regions are spaced farther apart in the presence of K. lactis Chd1, although this effect is somewhat stronger for nucleosomes within the gene body than for 5′ nucleosomes (Figures 2, B and C, Figure S3). Although the nucleosome repeat length increases by ∼1.5 bp in the presence of K. lactis Chd1 at the 5′ end, K. lactis Chd1 expands the average internucleosome spacing by 3 bp subsequent to the +3 nucleosome (Figures 2, B and C, Figure S2, Figure S3). Chd1 thus appears to be involved in the measurement of internucleosome distances, and evolutionary divergence between the S. cerevisiae and K. lactis copies results in altered measurement of linker length (see Discussion). It is important to note that other factors must play a role in establishing linker length, because the increase in nucleosome spacing seen with the introduction of K. lactis Chd1 does not fully account for the ∼15 bp longer average linkers seen in the K. lactis genome.

Bottom Line: In contrast, the K. lactis gene encoding the ATP-dependent remodeler Chd1 was found to direct longer internucleosomal spacing in S. cerevisiae, establishing that this remodeler is partially responsible for the relatively long internucleosomal spacing observed in K. lactis.By analyzing several chimeric proteins, we find that sequence differences that contribute to the spacing activity of this remodeler are dispersed throughout the coding sequence, but that the strongest spacing effect is linked to the understudied N-terminal end of Chd1.Taken together, our data find a role for sequence evolution of a chromatin remodeler in establishing quantitative aspects of the chromatin landscape in a species-specific manner.

View Article: PubMed Central - PubMed

Affiliation: Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Worcester, Massachusetts 01605.

No MeSH data available.


Related in: MedlinePlus