Genomic Nucleosome Organization Reconstituted with Pure Proteins

Krietenstein, Nils; Wal, Megha; Watanabe, Shinya; Park, Bong Soo; Peterson, Craig L.; Pugh, B. Franklin; Korber, Philipp

doi:10.1016/j.cell.2016.09.045

Cited by 255 publications

(464 citation statements)

References 73 publications

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“…In humans, the NRL ranges from ~178–205 bp, depending on histone modification state (Valouev et al, 2011), with activation marks having the shortest NRL. Thus, the underlying DNA sequence (Segal and Widom, 2009) and/or the proteins that interact with histones, such as Isw1a (Krietenstein et al, 2016), are more likely to specify this property.…”

Section: Discussionmentioning

confidence: 99%

Resetting the Yeast Epigenome with Human Nucleosomes

Truong

Boeke

2017

Cell

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Summary Humans and yeast are separated by a billion years of evolution, yet their conserved histones retain central roles in gene regulation. Here, we “reset” yeast to use core human nucleosomes in lieu of their own – a rare event taking twenty days – which initially only worked with variant H3.1. The cells adapt by acquiring suppressor mutations in cell-division genes, or by acquiring certain aneuploid states. Converting five histone residues to their yeast counterparts restored robust growth. We reveal that humanized nucleosomes are positioned according to endogenous yeast DNA sequence and chromatin-remodeling network, as judged by a yeast-like nucleosome repeat length. However, human nucleosomes have higher DNA occupancy, globally reduce RNA content, and slow adaptation to new conditions by delaying chromatin remodeling. These humanized yeasts (including H3.3) pose fundamental new questions about how chromatin is linked to many cell processes, and provides a platform to study histone variants via yeast epigenome reprogramming.

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Section: Discussionmentioning

confidence: 99%

Resetting the Yeast Epigenome with Human Nucleosomes

Truong

Boeke

2017

Cell

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“…(9). Similarly, INO80 has been shown to help position the +1 nucleosome [54], suggesting that INO80 may act as an additional energy barrier at TSS. Thus, incorporation of INO80 ChIP-seq information into the sequence model may help improve the prediction of nucleosome landscape.…”

Section: Discussionmentioning

confidence: 99%

“…Thus, incorporation of INO80 ChIP-seq information into the sequence model may help improve the prediction of nucleosome landscape. Lastly, it is known that ISW1 can tighten the spacing in nucleosome arrays downstream of TSS [54]. A plausible hypothesis is that ISW1 increases the effective chemical potential so that the nucleosomes in the region are more tightly packed.…”

Section: Discussionmentioning

confidence: 99%

A unified computational framework for modeling genome-wide nucleosome landscape

Finnegan

Song

2018

Phys. Biol.

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Nucleosomes form the fundamental building blocks of eukaryotic chromatin, and previous attempts to understand the principles governing their genome-wide distribution have spurred much interest and debate in biology. In particular, the precise role of DNA sequence in shaping local chromatin structure has been controversial. This paper rigorously quantifies the contribution of hitherto-debated sequence features – including G+C content, 10.5-bp periodicity, and poly(dA:dT) tracts – to three distinct aspects of genome-wide nucleosome landscape: occupancy, translational positioning and rotational positioning. Our computational framework simultaneously learns nucleosome number and nucleosome-positioning energy from genome-wide nucleosome maps. In contrast to other previous studies, our model can predict both in-vitro and in-vivo nucleosome maps in S. cerevisiae. We find that although G+C content is the primary determinant of MNase-derived nucleosome occupancy, MNase digestion biases may substantially influence this GC dependence. By contrast, poly(dA:dT) tracts are seen to deter nucleosome formation, regardless of the experimental method used. We further show that the 10.5-bp nucleotide periodicity facilitates rotational but not translational positioning. Applying our method to in-vivo nucleosome maps demonstrates that, for a subset of genes, the regularly-spaced nucleosome arrays observed around transcription start sites can be partially recapitulated by DNA sequence alone. Finally, in-vivo nucleosome occupancy derived from MNase-seq experiments around transcription termination sites can be mostly explained by the genomic sequence. Implications of these results and potential extensions of the proposed computational framework are discussed.

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“…One example where sequence context appears paramount is for the INO80 remodeler. In a genome-wide study of nucleosome positioning in Saccharomyces cerevisiae , INO80 was discovered to be responsible for the precise positioning of +1 nucleosomes, and could recapitulate in vivo nucleosome positions through DNA sequence alone 6 . Although further work will be needed to tease out the relationship between DNA sequence and INO80 action, nucleosome positioning by INO80 correlated with a predicted greater twist of DNA over the dyad of the +1 nucleosome, suggesting a mechanism of responding to DNA shape on the nucleosome.…”

Section: Introductionmentioning

confidence: 99%

The Sequence of Nucleosomal DNA Modulates Sliding by the Chd1 Chromatin Remodeler

Winger

Bowman

2017

Journal of Molecular Biology

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Chromatin remodelers are ATP-dependent enzymes that are critical for reorganizing and repositioning nucleosomes in concert with many basic cellular processes. For the Chromodomain Helicase DNA Binding Protein 1 (Chd1) remodeler, nucleosome sliding has been shown to depend on DNA flanking the nucleosome, transcription factor binding at the nucleosome edge, and the presence of the histone H2A/H2B dimer on the entry side. Here we report that Chd1 is also sensitive to the sequence of DNA within the nucleosome, and slides nucleosomes made with the 601 Widom positioning sequence asymmetrically. Kinetic and equilibrium experiments show that poly(dA:dT) tracts perturb remodeling reactions if within one and a half helical turns of superhelix location 2 (SHL2), where the Chd1 ATPase engages nucleosomal DNA. These sequence-dependent effects do not rely on the Chd1 DNA-binding domain and are not due to differences in nucleosome affinity. Using site-specific cross-linking, we show that internal poly(dA:dT) tracts do not block engagement of the ATPase motor with SHL2, yet they promote multiple translational positions of DNA with respect to both Chd1 and the histone core. We speculate that Chd1 senses the sequence-dependent response of DNA as the remodeler ATPase perturbs the duplex at SHL2. These results suggest that the sequence sensitivity of histones and remodelers occurs at unique segments of DNA on the nucleosome, and therefore can work together or in opposition to determine nucleosome positions throughout the genome.

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Genomic Nucleosome Organization Reconstituted with Pure Proteins

Cited by 255 publications

References 73 publications

Resetting the Yeast Epigenome with Human Nucleosomes

Resetting the Yeast Epigenome with Human Nucleosomes

A unified computational framework for modeling genome-wide nucleosome landscape

The Sequence of Nucleosomal DNA Modulates Sliding by the Chd1 Chromatin Remodeler

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