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GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p.

Dekker J - Genome Biol. (2007)

Bottom Line: We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription.Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.

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Affiliation: Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Plantation Street, Worcester, MA 01605-4321, USA. job.dekker@umassmed.edu

ABSTRACT

Background: Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood.

Results: We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.

Conclusion: We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.

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GC-rich and AT-rich genes differ in levels of acetylation of specific histone tail residues in wild-type cells. Genes were grouped in six groups dependent on the average base composition of the 4 kb region centered on the start site of the gene. For each group average levels of acetylation of different histone tail residues were determined using a dataset obtained by Kurdistani and co-workers [36]. (a-d) GC-rich genes display higher levels of H4K8, H4K12, H3K9 and H3K18 acetylation compared to AT-rich genes. (e) Comparison of the average levels of 11 histone modifications for GC-rich genes (GC > 40.4%) and AT-rich genes (GC < 36.6%). H3 and H4 acetylation is higher for GC-rich genes, whereas H2A and H2B acetylation is not different for the two types of isochore domains.
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Figure 2: GC-rich and AT-rich genes differ in levels of acetylation of specific histone tail residues in wild-type cells. Genes were grouped in six groups dependent on the average base composition of the 4 kb region centered on the start site of the gene. For each group average levels of acetylation of different histone tail residues were determined using a dataset obtained by Kurdistani and co-workers [36]. (a-d) GC-rich genes display higher levels of H4K8, H4K12, H3K9 and H3K18 acetylation compared to AT-rich genes. (e) Comparison of the average levels of 11 histone modifications for GC-rich genes (GC > 40.4%) and AT-rich genes (GC < 36.6%). H3 and H4 acetylation is higher for GC-rich genes, whereas H2A and H2B acetylation is not different for the two types of isochore domains.

Mentions: We again divided all genes into six groups based on their base composition, exactly as described above. For each group we determined the average level of each of 11 histone modifications (Figure 2a-d; Additional data file 3). We found that 4 out of 11 modifications (histone H4 Lys8 (H4K8) and Lys12 (H4K12), and histone H3 Lys9 (H3K9) and Lys18 (H3K18)) are enriched in GC-rich chromatin and depleted in AT-rich chromatin. The levels of the remaining seven modifications were not clearly correlated with base composition (histone H4 Lys16 (H4K16), histone H3 Lys14 (H3K14), LysK23 (H3K23) and Lys27 (H3K27), histone H2A Lys7 (H2AK7), and histone H2B Lys11 (H2BK11) and Lys16 (H2BK16); Additional data file 3). Interestingly, modifications of both H3 and H4 are correlated with base-composition, whereas modifications of H2A and H2B are not. These results demonstrate that GC- and AT-rich chromatin domains display distinct levels of H3 and H4 acetylation (Figure 2e) and provide additional evidence for structural and functional differences of isochore domains in yeast.


GC- and AT-rich chromatin domains differ in conformation and histone modification status and are differentially modulated by Rpd3p.

Dekker J - Genome Biol. (2007)

GC-rich and AT-rich genes differ in levels of acetylation of specific histone tail residues in wild-type cells. Genes were grouped in six groups dependent on the average base composition of the 4 kb region centered on the start site of the gene. For each group average levels of acetylation of different histone tail residues were determined using a dataset obtained by Kurdistani and co-workers [36]. (a-d) GC-rich genes display higher levels of H4K8, H4K12, H3K9 and H3K18 acetylation compared to AT-rich genes. (e) Comparison of the average levels of 11 histone modifications for GC-rich genes (GC > 40.4%) and AT-rich genes (GC < 36.6%). H3 and H4 acetylation is higher for GC-rich genes, whereas H2A and H2B acetylation is not different for the two types of isochore domains.
© Copyright Policy - open-access
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC2394764&req=5

Figure 2: GC-rich and AT-rich genes differ in levels of acetylation of specific histone tail residues in wild-type cells. Genes were grouped in six groups dependent on the average base composition of the 4 kb region centered on the start site of the gene. For each group average levels of acetylation of different histone tail residues were determined using a dataset obtained by Kurdistani and co-workers [36]. (a-d) GC-rich genes display higher levels of H4K8, H4K12, H3K9 and H3K18 acetylation compared to AT-rich genes. (e) Comparison of the average levels of 11 histone modifications for GC-rich genes (GC > 40.4%) and AT-rich genes (GC < 36.6%). H3 and H4 acetylation is higher for GC-rich genes, whereas H2A and H2B acetylation is not different for the two types of isochore domains.
Mentions: We again divided all genes into six groups based on their base composition, exactly as described above. For each group we determined the average level of each of 11 histone modifications (Figure 2a-d; Additional data file 3). We found that 4 out of 11 modifications (histone H4 Lys8 (H4K8) and Lys12 (H4K12), and histone H3 Lys9 (H3K9) and Lys18 (H3K18)) are enriched in GC-rich chromatin and depleted in AT-rich chromatin. The levels of the remaining seven modifications were not clearly correlated with base composition (histone H4 Lys16 (H4K16), histone H3 Lys14 (H3K14), LysK23 (H3K23) and Lys27 (H3K27), histone H2A Lys7 (H2AK7), and histone H2B Lys11 (H2BK11) and Lys16 (H2BK16); Additional data file 3). Interestingly, modifications of both H3 and H4 are correlated with base-composition, whereas modifications of H2A and H2B are not. These results demonstrate that GC- and AT-rich chromatin domains display distinct levels of H3 and H4 acetylation (Figure 2e) and provide additional evidence for structural and functional differences of isochore domains in yeast.

Bottom Line: We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription.Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.

View Article: PubMed Central - HTML - PubMed

Affiliation: Program in Gene Function and Expression and Department of Biochemistry and Molecular Pharmacology, University of Massachusetts Medical School, Plantation Street, Worcester, MA 01605-4321, USA. job.dekker@umassmed.edu

ABSTRACT

Background: Base-composition varies throughout the genome and is related to organization of chromosomes in distinct domains (isochores). Isochore domains differ in gene expression levels, replication timing, levels of meiotic recombination and chromatin structure. The molecular basis for these differences is poorly understood.

Results: We have compared GC- and AT-rich isochores of yeast with respect to chromatin conformation, histone modification status and transcription. Using 3C analysis we show that, along chromosome III, GC-rich isochores have a chromatin structure that is characterized by lower chromatin interaction frequencies compared to AT-rich isochores, which may point to a more extended chromatin conformation. In addition, we find that throughout the genome, GC-rich and AT-rich genes display distinct levels of histone modifications. Interestingly, elimination of the histone deacetylase Rpd3p differentially affects conformation of GC- and AT-rich domains. Further, deletion of RPD3 activates expression of GC-rich genes more strongly than AT-rich genes. Analyses of effects of the histone deacetylase inhibitor trichostatin A, global patterns of Rpd3p binding and effects of deletion of RPD3 on histone H4 acetylation confirmed that conformation and activity of GC-rich chromatin are more sensitive to Rpd3p-mediated deacetylation than AT-rich chromatin.

Conclusion: We find that GC-rich and AT-rich chromatin domains display distinct chromatin conformations and are marked by distinct patterns of histone modifications. We identified the histone deacetylase Rpd3p as an attenuator of these base composition-dependent differences in chromatin status. We propose that GC-rich chromatin domains tend to occur in a more active conformation and that Rpd3p activity represses this propensity throughout the genome.

Show MeSH