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ISWI and CHD chromatin remodelers bind promoters but act in gene bodies.

Zentner GE, Tsukiyama T, Henikoff S - PLoS Genet. (2013)

Bottom Line: Although these remodelers act in gene bodies, we find that they are also highly enriched at nucleosome-depleted regions (NDRs), where they bind to extended regions of DNA adjacent to particular transcription factors.Surprisingly, catalytically inactive remodelers show similar binding patterns.We find that remodeler occupancy at NDRs and gene bodies is associated with nucleosome turnover and transcriptional elongation rate, suggesting that remodelers act on regions of transient nucleosome unwrapping or depletion within gene bodies subsequent to transcriptional elongation.

View Article: PubMed Central - PubMed

Affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

ABSTRACT
ATP-dependent nucleosome remodelers influence genetic processes by altering nucleosome occupancy, positioning, and composition. In vitro, Saccharomyces cerevisiae ISWI and CHD remodelers require ∼30-85 bp of extranucleosomal DNA to reposition nucleosomes, but linker DNA in S. cerevisiae averages <20 bp. To address this discrepancy between in vitro and in vivo observations, we have mapped the genomic distributions of the yeast Isw1, Isw2, and Chd1 remodelers at base-pair resolution on native chromatin. Although these remodelers act in gene bodies, we find that they are also highly enriched at nucleosome-depleted regions (NDRs), where they bind to extended regions of DNA adjacent to particular transcription factors. Surprisingly, catalytically inactive remodelers show similar binding patterns. We find that remodeler occupancy at NDRs and gene bodies is associated with nucleosome turnover and transcriptional elongation rate, suggesting that remodelers act on regions of transient nucleosome unwrapping or depletion within gene bodies subsequent to transcriptional elongation.

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ISWI and CHD remodeler binding is positively associated with histone turnover and transcription rate.(A) Heat maps of log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by gene expression. (B) Heat maps of log2(nucleosome turnover) and log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by average nucleosome turnover across the entire 2-kb window. (C) Aggregate plots of Chd1, Isw1, and Isw2 log2(IP/input) signal ±1 kb of verified ORF 5′ ends, separated by transcription rate in mRNA/hr [47].
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pgen-1003317-g007: ISWI and CHD remodeler binding is positively associated with histone turnover and transcription rate.(A) Heat maps of log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by gene expression. (B) Heat maps of log2(nucleosome turnover) and log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by average nucleosome turnover across the entire 2-kb window. (C) Aggregate plots of Chd1, Isw1, and Isw2 log2(IP/input) signal ±1 kb of verified ORF 5′ ends, separated by transcription rate in mRNA/hr [47].

Mentions: This model predicts that Chd1 and Isw1 association with gene bodies depends on transcription rate. As such, we would not expect to observe an association between remodeler binding and steady-state expression levels, as infrequently transcribed genes may yield mRNAs with long half-lives and vice versa [47]. Indeed, we observed no correlation between remodeler occupancy and steady-state gene expression (Figure 7A). Given that transcription is associated with histone turnover [48]–[52], we hypothesized that there might be a relationship between remodeler association and turnover. High turnover within ORF 5′ ends was postulated to reflect a requirement to maintain nucleosome depletion at promoters [51], which is achieved, at least in part, by TFs such as Abf1 and Reb1 and the SWI/SNF-family remodeler RSC [39], [41]. Comparison of histone turnover data with remodeler N-ChIP-seq data revealed a positive association between binding of remodelers to ORF 5′ ends and gene bodies and nucleosome turnover (Figure 7B). We also compared remodeler binding with transcription rate and found that highly transcribed genes were more highly bound by Isw1, Isw2, and Chd1 (Figure 7C). Taken together, these data suggest that Isw1 and Chd1 binding within gene bodies displaying high nucleosome turnover is a consequence of transcriptional elongation. While Isw2 generally does not bind gene bodies, its loss affects gene body nucleosomes, which shift to their thermodynamically favored positions in its absence [20]. The increased binding of Isw2 to the 5′ NDRs of highly transcribed genes may therefore reflect the increased nucleosome disruption caused by transcriptional elongation and, consequently, the increased requirement for the positioning activity of Isw2.


ISWI and CHD chromatin remodelers bind promoters but act in gene bodies.

Zentner GE, Tsukiyama T, Henikoff S - PLoS Genet. (2013)

ISWI and CHD remodeler binding is positively associated with histone turnover and transcription rate.(A) Heat maps of log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by gene expression. (B) Heat maps of log2(nucleosome turnover) and log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by average nucleosome turnover across the entire 2-kb window. (C) Aggregate plots of Chd1, Isw1, and Isw2 log2(IP/input) signal ±1 kb of verified ORF 5′ ends, separated by transcription rate in mRNA/hr [47].
© Copyright Policy
Related In: Results  -  Collection

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getmorefigures.php?uid=PMC3585014&req=5

pgen-1003317-g007: ISWI and CHD remodeler binding is positively associated with histone turnover and transcription rate.(A) Heat maps of log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by gene expression. (B) Heat maps of log2(nucleosome turnover) and log2(IP/input) signal for Chd1, Isw1, and Isw2 ±1 kb of verified ORF 5′ ranked descending by average nucleosome turnover across the entire 2-kb window. (C) Aggregate plots of Chd1, Isw1, and Isw2 log2(IP/input) signal ±1 kb of verified ORF 5′ ends, separated by transcription rate in mRNA/hr [47].
Mentions: This model predicts that Chd1 and Isw1 association with gene bodies depends on transcription rate. As such, we would not expect to observe an association between remodeler binding and steady-state expression levels, as infrequently transcribed genes may yield mRNAs with long half-lives and vice versa [47]. Indeed, we observed no correlation between remodeler occupancy and steady-state gene expression (Figure 7A). Given that transcription is associated with histone turnover [48]–[52], we hypothesized that there might be a relationship between remodeler association and turnover. High turnover within ORF 5′ ends was postulated to reflect a requirement to maintain nucleosome depletion at promoters [51], which is achieved, at least in part, by TFs such as Abf1 and Reb1 and the SWI/SNF-family remodeler RSC [39], [41]. Comparison of histone turnover data with remodeler N-ChIP-seq data revealed a positive association between binding of remodelers to ORF 5′ ends and gene bodies and nucleosome turnover (Figure 7B). We also compared remodeler binding with transcription rate and found that highly transcribed genes were more highly bound by Isw1, Isw2, and Chd1 (Figure 7C). Taken together, these data suggest that Isw1 and Chd1 binding within gene bodies displaying high nucleosome turnover is a consequence of transcriptional elongation. While Isw2 generally does not bind gene bodies, its loss affects gene body nucleosomes, which shift to their thermodynamically favored positions in its absence [20]. The increased binding of Isw2 to the 5′ NDRs of highly transcribed genes may therefore reflect the increased nucleosome disruption caused by transcriptional elongation and, consequently, the increased requirement for the positioning activity of Isw2.

Bottom Line: Although these remodelers act in gene bodies, we find that they are also highly enriched at nucleosome-depleted regions (NDRs), where they bind to extended regions of DNA adjacent to particular transcription factors.Surprisingly, catalytically inactive remodelers show similar binding patterns.We find that remodeler occupancy at NDRs and gene bodies is associated with nucleosome turnover and transcriptional elongation rate, suggesting that remodelers act on regions of transient nucleosome unwrapping or depletion within gene bodies subsequent to transcriptional elongation.

View Article: PubMed Central - PubMed

Affiliation: Basic Sciences Division, Fred Hutchinson Cancer Research Center, Seattle, Washington, USA.

ABSTRACT
ATP-dependent nucleosome remodelers influence genetic processes by altering nucleosome occupancy, positioning, and composition. In vitro, Saccharomyces cerevisiae ISWI and CHD remodelers require ∼30-85 bp of extranucleosomal DNA to reposition nucleosomes, but linker DNA in S. cerevisiae averages <20 bp. To address this discrepancy between in vitro and in vivo observations, we have mapped the genomic distributions of the yeast Isw1, Isw2, and Chd1 remodelers at base-pair resolution on native chromatin. Although these remodelers act in gene bodies, we find that they are also highly enriched at nucleosome-depleted regions (NDRs), where they bind to extended regions of DNA adjacent to particular transcription factors. Surprisingly, catalytically inactive remodelers show similar binding patterns. We find that remodeler occupancy at NDRs and gene bodies is associated with nucleosome turnover and transcriptional elongation rate, suggesting that remodelers act on regions of transient nucleosome unwrapping or depletion within gene bodies subsequent to transcriptional elongation.

Show MeSH
Related in: MedlinePlus