A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization

Gkikopoulos, Triantaffyllos; Schofield, Pietà; Singh, Vijender; Pinskaya, Marina; Mellor, Jane; Smolle, Michaela; Workman, Jerry L.; Barton, Geoffrey J.; Owen-Hughes, Tom

doi:10.1126/science.1206097

Cited by 271 publications

(370 citation statements)

References 30 publications

(31 reference statements)

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“…pattern requires whole-cell extract and ATP (13) and (ii) a combined knockout of several remodelers shows a clear phenotype in the average nucleosome pattern, whereas individual knockouts have mild effects (14). Given that both observations are at a physiological histone-DNA ratio, they can be rationalized kinetically only within the active SNG model: As previously pointed out (22), the intrinsic dynamics of nucleosomes, i.e., fluctuationinduced unbinding and diffusion along DNA, are too slow to equilibrate their positions on the relevant timescales of cell division or in vitro experiments.…”

Section: Discussionmentioning

confidence: 99%

“…Within this framework, is there a single model that consistently explains all patterns? Second, recent experiments have shown in vitro (13) and in vivo (14) that the formation of the native nucleosome pattern requires the action of remodeling enzymes. Moreover, reduction of the histone-DNA ratio in vitro (13) or in vivo (15) does not lead to a concomitant increase in the typical nucleosome spacing, as would be expected for statistical positioning.…”

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confidence: 99%

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Toward a unified physical model of nucleosome patterns flanking transcription start sites

Möbius

Osberg

Tsankov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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Recent genome-wide maps of nucleosome positions in different eukaryotes revealed patterns around transcription start sites featuring a nucleosome-free region flanked by a periodic modulation of the nucleosome density. For Saccharomyces cerevisiae, the average in vivo pattern was previously shown to be quantitatively described by a "nucleosome gas" model based on the statistical positioning mechanism. However, this simple physical description is challenged by the fact that the pattern differs quantitatively between species and by recent experiments that appear incompatible with statistical positioning, indicating important roles for chromatin remodelers. We undertake a data-driven search for a unified physical model to describe the nucleosome patterns of 12 yeast species and also consider an extension of the model to capture remodeling effects. We are led to a nucleosome gas that takes into account nucleosome breathing, i.e., transient unwrapping of nucleosomal DNA segments. This known biophysical property of nucleosomes rationalizes a "pressure"-induced dependence of the effective nucleosome size that is suggested by the data. By fitting this model to the data, we find an average energy cost for DNA unwrapping consistent with previous biophysical experiments. Although the available data are not sufficient to reconstruct chromatin remodeling mechanisms, a minimal model extension by one mechanism yields an "active nucleosome gas" that can rationalize the behavior of systems with reduced histone-DNA ratio and remodeler knockouts. We therefore establish a basis for a physical description of nucleosome patterns that can serve as a null model for sequence-specific effects at individual genes and in models of transcription regulation.nucleosome maps | chromatin structure | quantitative biology

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Toward a unified physical model of nucleosome patterns flanking transcription start sites

Möbius

Osberg

Tsankov

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

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“…Chd1 has been linked to various transcription-related processes, including regulation of nucleosome positioning at the 5′ end of transcribed genes (15,16), suppression of cryptic transcription (17,18), transcriptional elongation (17,19,20), and coupling of transcription with splicing (21). We have previously described Chd1 as a gene up-regulated in multiple mouse stem and progenitor cell types (22,23).…”

mentioning

confidence: 99%

Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription

Koh

Lizama

Wong

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

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Lineage specification during development involves reprogramming of transcriptional states, but little is known about how this is regulated in vivo. The chromatin remodeler chomodomain helicase DNA-binding protein 1 (Chd1) promotes an elevated transcriptional output in mouse embryonic stem cells. Here we report that endothelial-specific deletion of Chd1 leads to loss of definitive hematopoietic progenitors, anemia, and lethality by embryonic day (E)15.5. Mutant embryos contain normal numbers of E10.5 intraaortic hematopoietic clusters that express Runx1 and Kit, but these clusters undergo apoptosis and fail to mature into blood lineages in vivo and in vitro. Hematopoietic progenitors emerging from the aorta have an elevated transcriptional output relative to structural endothelium, and this elevation is Chd1-dependent. In contrast, hematopoietic-specific deletion of Chd1 using Vav-Cre has no apparent phenotype. Our results reveal a new paradigm of regulation of a developmental transition by elevation of global transcriptional output that is critical for hemogenesis and may play roles in other contexts.

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“…The in vitro nucleosome maps were generated by reconstituting nucleosomes on yeast genomic DNA, in the presence or absence of trans-acting factors, represented by cell extracts or ATP-dependent chromatin remodelers (Kaplan et al 2009;Zhang et al 2009Zhang et al , 2011b. Such experiments revealed that trans-acting factors, rather than the DNA sequence preferences of nucleosomes (Zhang et al 2009(Zhang et al , 2011bGkikopoulos et al 2011;Hughes et al 2012;Yen et al 2012), mainly underlie the characteristic nucleosome array downstream from TSSs. This stands in contrast to the regulatory nucleosome-depleted regions upstream of TSSs, which were found to be intrinsically unfavorable to nucleosome formation (Kaplan et al 2009;Zhang et al 2009).…”

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confidence: 99%

DNA-guided establishment of nucleosome patterns within coding regions of a eukaryotic genome

et al. 2015

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A conserved hallmark of eukaryotic chromatin architecture is the distinctive array of well-positioned nucleosomes downstream from transcription start sites (TSS). Recent studies indicate that trans-acting factors establish this stereotypical array. Here, we present the first genome-wide in vitro and in vivo nucleosome maps for the ciliate Tetrahymena thermophila. In contrast with previous studies in yeast, we find that the stereotypical nucleosome array is preserved in the in vitro reconstituted map, which is governed only by the DNA sequence preferences of nucleosomes. Remarkably, this average in vitro pattern arises from the presence of subsets of nucleosomes, rather than the whole array, in individual Tetrahymena genes. Variation in GC content contributes to the positioning of these sequence-directed nucleosomes and affects codon usage and amino acid composition in genes. Given that the AT-rich Tetrahymena genome is intrinsically unfavorable for nucleosome formation, we propose that these “seed” nucleosomes—together with trans-acting factors—may facilitate the establishment of nucleosome arrays within genes in vivo, while minimizing changes to the underlying coding sequences.

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A Role for Snf2-Related Nucleosome-Spacing Enzymes in Genome-Wide Nucleosome Organization

Cited by 271 publications

References 30 publications

Toward a unified physical model of nucleosome patterns flanking transcription start sites

Toward a unified physical model of nucleosome patterns flanking transcription start sites

Emergence of hematopoietic stem and progenitor cells involves a Chd1-dependent increase in total nascent transcription

DNA-guided establishment of nucleosome patterns within coding regions of a eukaryotic genome

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