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Topoisomerase II regulates yeast genes with singular chromatin architectures.

Nikolaou C, Bermúdez I, Manichanh C, García-Martinez J, Guigó R, Pérez-Ortín JE, Roca J - Nucleic Acids Res. (2013)

Bottom Line: To uncover this, we carried out a genomic transcription run-on shortly after the thermal inactivation of topo II.We identified a modest number of genes not involved in the general stress response but strictly dependent on topo II.These genes present distinctive functional and structural traits in comparison with the genome average.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Institute of Barcelona, CSIC, 08028 Barcelona, Spain, Department of Biology, University of Crete, 71409 Heraklion, Greece, Department of Genetics and ERI Biotecmed, University of Valencia, 46100 Burjassot, Spain, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain and Department of Biochemistry and Molecular Biology and ERI Biotecmed, University of Valencia, 46100 Burjassot, Spain.

ABSTRACT
Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly replicated chromosomes and the main relaxase of nucleosomal DNA. Apart from these general tasks, topo II participates in more specialized functions. In mammals, topo IIα interacts with specific RNA polymerases and chromatin-remodeling complexes, whereas topo IIβ regulates developmental genes in conjunction with chromatin remodeling and heterochromatin transitions. Here we show that in budding yeast, topo II regulates the expression of specific gene subsets. To uncover this, we carried out a genomic transcription run-on shortly after the thermal inactivation of topo II. We identified a modest number of genes not involved in the general stress response but strictly dependent on topo II. These genes present distinctive functional and structural traits in comparison with the genome average. Yeast topo II is a positive regulator of genes with well-defined promoter architecture that associates to chromatin remodeling complexes; it is a negative regulator of genes extremely hypo-acetylated with complex promoters and undefined nucleosome positioning, many of which are involved in polyamine transport. These findings indicate that yeast topo II operates on singular chromatin architectures to activate or repress DNA transcription and that this activity produces functional responses to ensure chromatin stability.

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Histone modification pattern of deregulated genes. Gene subsets downregulated (A) and upregulated (B) after topo II inactivation were analyzed for histone modification enrichments in ChromatinDB (58). Relative enrichment (gene subset average compared with the total yeast average) of each indicated modification was evaluated based on a Wilcoxon rank sum test for both gene promoters and the ORF regions. Stars denote significant enrichment or depletion (P < 0.001).
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gkt707-F6: Histone modification pattern of deregulated genes. Gene subsets downregulated (A) and upregulated (B) after topo II inactivation were analyzed for histone modification enrichments in ChromatinDB (58). Relative enrichment (gene subset average compared with the total yeast average) of each indicated modification was evaluated based on a Wilcoxon rank sum test for both gene promoters and the ORF regions. Stars denote significant enrichment or depletion (P < 0.001).

Mentions: We examined the chromatin landscapes of the genes deregulated on topo II inactivation with ChromatinDB, a web-based application that warehouses genome-wide patterns of histone modifications for S. cerevisiae (58). On one side, the average pattern of modifications in downregulated genes was not different from the one found in most yeast genes (Figure 6A). Only a significant increase of H2AZK14 acetylation and H3K4 methylation was observed in their promoter and ORF regions, respectively. These modifications contrasted with those typically found in genes downregulated by general stress, which tend to be hypo-acetylated at their promoter regions (Supplementary Figure S6). On the other side, upregulated genes presented a distinctive landscape compared with the genome average (Figure 6B). They exhibited a significant reduction in histone acetylation, at both the promoters and the ORF regions. Di-methylation of H3K36 was also significantly reduced in promoters and ORF regions. The occupancy of H2AZ, a histone variant commonly found in nucleosomes around the TSS, was significantly enriched downstream the TSS although depleted upstream from it. This modification pattern of upregulated genes highly contrasted also with the patterns found in genes upregulated by general stress conditions and in TATA-containing genes (Supplementary Figure S6).Figure 6.


Topoisomerase II regulates yeast genes with singular chromatin architectures.

Nikolaou C, Bermúdez I, Manichanh C, García-Martinez J, Guigó R, Pérez-Ortín JE, Roca J - Nucleic Acids Res. (2013)

Histone modification pattern of deregulated genes. Gene subsets downregulated (A) and upregulated (B) after topo II inactivation were analyzed for histone modification enrichments in ChromatinDB (58). Relative enrichment (gene subset average compared with the total yeast average) of each indicated modification was evaluated based on a Wilcoxon rank sum test for both gene promoters and the ORF regions. Stars denote significant enrichment or depletion (P < 0.001).
© Copyright Policy - creative-commons
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3814376&req=5

gkt707-F6: Histone modification pattern of deregulated genes. Gene subsets downregulated (A) and upregulated (B) after topo II inactivation were analyzed for histone modification enrichments in ChromatinDB (58). Relative enrichment (gene subset average compared with the total yeast average) of each indicated modification was evaluated based on a Wilcoxon rank sum test for both gene promoters and the ORF regions. Stars denote significant enrichment or depletion (P < 0.001).
Mentions: We examined the chromatin landscapes of the genes deregulated on topo II inactivation with ChromatinDB, a web-based application that warehouses genome-wide patterns of histone modifications for S. cerevisiae (58). On one side, the average pattern of modifications in downregulated genes was not different from the one found in most yeast genes (Figure 6A). Only a significant increase of H2AZK14 acetylation and H3K4 methylation was observed in their promoter and ORF regions, respectively. These modifications contrasted with those typically found in genes downregulated by general stress, which tend to be hypo-acetylated at their promoter regions (Supplementary Figure S6). On the other side, upregulated genes presented a distinctive landscape compared with the genome average (Figure 6B). They exhibited a significant reduction in histone acetylation, at both the promoters and the ORF regions. Di-methylation of H3K36 was also significantly reduced in promoters and ORF regions. The occupancy of H2AZ, a histone variant commonly found in nucleosomes around the TSS, was significantly enriched downstream the TSS although depleted upstream from it. This modification pattern of upregulated genes highly contrasted also with the patterns found in genes upregulated by general stress conditions and in TATA-containing genes (Supplementary Figure S6).Figure 6.

Bottom Line: To uncover this, we carried out a genomic transcription run-on shortly after the thermal inactivation of topo II.We identified a modest number of genes not involved in the general stress response but strictly dependent on topo II.These genes present distinctive functional and structural traits in comparison with the genome average.

View Article: PubMed Central - PubMed

Affiliation: Molecular Biology Institute of Barcelona, CSIC, 08028 Barcelona, Spain, Department of Biology, University of Crete, 71409 Heraklion, Greece, Department of Genetics and ERI Biotecmed, University of Valencia, 46100 Burjassot, Spain, Centre for Genomic Regulation (CRG), 08003 Barcelona, Spain and Department of Biochemistry and Molecular Biology and ERI Biotecmed, University of Valencia, 46100 Burjassot, Spain.

ABSTRACT
Eukaryotic topoisomerase II (topo II) is the essential decatenase of newly replicated chromosomes and the main relaxase of nucleosomal DNA. Apart from these general tasks, topo II participates in more specialized functions. In mammals, topo IIα interacts with specific RNA polymerases and chromatin-remodeling complexes, whereas topo IIβ regulates developmental genes in conjunction with chromatin remodeling and heterochromatin transitions. Here we show that in budding yeast, topo II regulates the expression of specific gene subsets. To uncover this, we carried out a genomic transcription run-on shortly after the thermal inactivation of topo II. We identified a modest number of genes not involved in the general stress response but strictly dependent on topo II. These genes present distinctive functional and structural traits in comparison with the genome average. Yeast topo II is a positive regulator of genes with well-defined promoter architecture that associates to chromatin remodeling complexes; it is a negative regulator of genes extremely hypo-acetylated with complex promoters and undefined nucleosome positioning, many of which are involved in polyamine transport. These findings indicate that yeast topo II operates on singular chromatin architectures to activate or repress DNA transcription and that this activity produces functional responses to ensure chromatin stability.

Show MeSH
Related in: MedlinePlus