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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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Promoter size and distribution of TFBS in genes deregulated after topo II inactivation. (A) Promoter size calculated as the length of the intergenic region extending upstream the TSS until the 5′ or 3′end of the most proximal gene. (B) Occurrence of bidirectional promoters defined as the intergenic regions (up to 600 bp in length) occupying the genomic space between two divergently transcribed genes (∼26% of 6059 genes). (C) Binding sites distribution for 126 yeast transcription factors in promoter regions of all yeast genes and the genes up- and downregulated by topo II inactivation.
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gkt707-F2: Promoter size and distribution of TFBS in genes deregulated after topo II inactivation. (A) Promoter size calculated as the length of the intergenic region extending upstream the TSS until the 5′ or 3′end of the most proximal gene. (B) Occurrence of bidirectional promoters defined as the intergenic regions (up to 600 bp in length) occupying the genomic space between two divergently transcribed genes (∼26% of 6059 genes). (C) Binding sites distribution for 126 yeast transcription factors in promoter regions of all yeast genes and the genes up- and downregulated by topo II inactivation.

Mentions: The size of gene promoters in S. cerevisiae is constrained by the short intergenic distance between ORFs, which is <500 bp on average (40). In this regard, the subset of genes downregulated by topo II deactivation had much shorter 5′ intergenic regions (300 bp on average) than the bulk of yeast genes. Conversely, the upregulated group presented 5′ intergenic regions longer than the global average (Figure 2A). Another striking trait of these intergenic regions concerned the occurrence of divergent gene transcription, which occurs in ∼26% of the global set of yeast genes. Both up- and downregulated gene subsets were highly enriched in divergent transcription genes (42 and 46%, respectively) (Figure 2B). Moreover, some genes in the upregulated group were divergent pairs (YAL054C and YAL053W, YLL061W and YLL062C, YPR156C and YPR157W), which suggested co-regulation from their bidirectional promoter region.Figure 2.


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)

Promoter size and distribution of TFBS in genes deregulated after topo II inactivation. (A) Promoter size calculated as the length of the intergenic region extending upstream the TSS until the 5′ or 3′end of the most proximal gene. (B) Occurrence of bidirectional promoters defined as the intergenic regions (up to 600 bp in length) occupying the genomic space between two divergently transcribed genes (∼26% of 6059 genes). (C) Binding sites distribution for 126 yeast transcription factors in promoter regions of all yeast genes and the genes up- and downregulated by topo II inactivation.
© Copyright Policy - creative-commons
Related In: Results  -  Collection

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

gkt707-F2: Promoter size and distribution of TFBS in genes deregulated after topo II inactivation. (A) Promoter size calculated as the length of the intergenic region extending upstream the TSS until the 5′ or 3′end of the most proximal gene. (B) Occurrence of bidirectional promoters defined as the intergenic regions (up to 600 bp in length) occupying the genomic space between two divergently transcribed genes (∼26% of 6059 genes). (C) Binding sites distribution for 126 yeast transcription factors in promoter regions of all yeast genes and the genes up- and downregulated by topo II inactivation.
Mentions: The size of gene promoters in S. cerevisiae is constrained by the short intergenic distance between ORFs, which is <500 bp on average (40). In this regard, the subset of genes downregulated by topo II deactivation had much shorter 5′ intergenic regions (300 bp on average) than the bulk of yeast genes. Conversely, the upregulated group presented 5′ intergenic regions longer than the global average (Figure 2A). Another striking trait of these intergenic regions concerned the occurrence of divergent gene transcription, which occurs in ∼26% of the global set of yeast genes. Both up- and downregulated gene subsets were highly enriched in divergent transcription genes (42 and 46%, respectively) (Figure 2B). Moreover, some genes in the upregulated group were divergent pairs (YAL054C and YAL053W, YLL061W and YLL062C, YPR156C and YPR157W), which suggested co-regulation from their bidirectional promoter region.Figure 2.

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