Measuring DNA mechanics on the genome scale

Basu, Aakash; Bobrovnikov, Dmitriy G.; Qureshi, Zan; Kayikcioglu, Tunc; Ngo, Thuy; Ranjan, Anand; Eustermann, Sebastian; Cieza, Basilio; Morgan, Michael T.; Hejna, Miroslav; Rube, H. Tomas; Hopfner, Karl‐Peter; Wolberger, Cynthia; Song, Jun; Ha, Taekjip

doi:10.1101/2020.08.17.255042

Cited by 14 publications

(36 citation statements)

References 37 publications

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“…Both dynamic flexibility as well as static bends may contribute to intrinsic cyclizability as noted previously 31 . Speculatively, the NN-NN helical separation extent contributes to intrinsic cyclizability mainly by altering the static bent structure of DNA and determining whether static bends add in or out of phase.…”

Section: Sequence Features That Influence Dna Cyclizabilitymentioning

confidence: 60%

“…Codon usage frequency in S. cerevisiae leads to a higher overall predicted intrinsic cyclizability than if all synonymous codons were used with equal frequency. In fact, experimental measurements roughly agree with this trend, but high noise in the data obscured a definitive conclusion 31 . This, however, is not generally true for all organisms (supplementary note 21).…”

Section: Dna Mechanics and Amino Acid Sequence Are Linkedmentioning

confidence: 77%

“…Although the relative shapes agree, absolute values of intrinsic cyclizability do not agree between prediction and measurement. This is because measured intrinsic cyclizability is defined only up to an additive constant which depends on other sequences present in the library 31 .…”

Section: Models To Predict Intrinsic Cyclizabilitymentioning

confidence: 99%

“…We recently reported the a high-throughput experimental method called loop-seq to determine the cyclization propensity of as many as ~90,000 different specified 50 bp DNA sequences at a time 31 . DNA fragments immobilized on a surface via biotin-streptavidin linkage are permitted to briefly cyclize in situ.…”

Section: Introductionmentioning

confidence: 99%

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Deciphering the mechanical code of genome and epigenome

Basu

Cieza

et al. 2020

Preprint

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Sequence features have long been known to influence the local mechanical properties and shapes of DNA. However, a mechanical code (i.e. a comprehensive mapping between DNA sequence and mechanical properties), if it exists, has been difficult to experimentally determine because direct means of measuring the mechanical properties of DNA are typically limited in throughput. Here we use Loop-seq – a recently developed technique to measure the intrinsic cyclizabilities (a proxy for bendability) of DNA fragments in genomic-scale throughput – to characterize the mechanical code. We tabulate how DNA sequence features (distribution patterns of all possible dinucleotides and dinucleotide pairs) influence intrinsic cyclizability, and build a linear model to predict intrinsic cyclizability from sequence. Using our model, we predict that DNA mechanical landscape shapes nucleosome organization around the promoters of various organisms and at the binding site of the transcription factor CTCF, and that hyperperiodic DNA in C. elegans leads to globally curved DNA segments. By performing loop-seq on random libraries in the presence or absence of CpG methylation, we show that CpG methylation leads to global stiffening of DNA in a wide sequence context, and predict based on our model that CpG methylation widely changes the mechanical landscape around mouse promoters. It suggests how epigenetic modifications of DNA might alter gene expression and mediate cellular adaptation by affecting critical processes around promoters that require mechanical deformations of DNA, such as nucleosome organization and transcription initiation. Finally, we show that the genetic code and the mechanical code are linked: sequence-dependent mechanical properties of coding DNA constrains the amino acid sequence despite the degeneracy in the genetic code. Our measurements explain why the pattern of nucleosome organization along genes influences the distribution of amino acids in the translated polypeptide.

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Section: Sequence Features That Influence Dna Cyclizabilitymentioning

confidence: 60%

Section: Dna Mechanics and Amino Acid Sequence Are Linkedmentioning

confidence: 77%

Section: Models To Predict Intrinsic Cyclizabilitymentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Deciphering the mechanical code of genome and epigenome

Basu

Cieza

et al. 2020

Preprint

Self Cite

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“…4c). Intriguingly, a similarly rigid promoter DNA motif at the same distance in respect to the +1 nucleosome was also identified in a parallel study, where DNA mechanics were measured experimentally on a genomic scale via library-based DNA circularization assays 54 .…”

Section: Resultsmentioning

confidence: 85%

Genome information processing by the INO80 chromatin remodeler positions nucleosomes

Oberbeckmann

Krietenstein

Niebauer

et al. 2020

Preprint

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The fundamental molecular determinants by which ATP-dependent chromatin remodelers organize nucleosomes across eukaryotic genomes remain largely elusive. Here, chromatin reconstitutions on physiological, whole-genome templates reveal how remodelers read and translate genomic information into nucleosome positions. Using the yeast genome and the multi-subunit INO80 remodeler as a paradigm, we identify DNA shape/mechanics encoded signature motifs as sufficient for nucleosome positioning and distinct from known DNA sequence preferences of histones. INO80 processes such information through an allosteric interplay between its core- and Arp8-modules that probes mechanical properties of nucleosomal and linker DNA. At promoters, INO80 integrates this readout of DNA shape/mechanics with a readout of co-evolved sequence motifs via interaction with general regulatory factors bound to these motifs. Our findings establish a molecular mechanism for robust and yet adjustable +1 nucleosome positioning and, more generally, remodelers as information processing hubs that enable active organization and allosteric regulation of the first level of chromatin.

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A deformation energy model reveals sequence-dependent property of nucleosome positioning

et al. 2021

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We present a deformation energy model for predicting nucleosome positioning, in which a position-dependent structural parameter set derived from crystal structures of nucleosomes was used to calculate the DNA deformation energy. The model is successful in predicting nucleosome occupancy genome-wide in budding yeast, nucleosome free energy, and rotational positioning of nucleosomes. Our model also indicates that the genomic regions underlying the MNase-sensitive nucleosomes in budding yeast have high deformation energy and, consequently, low nucleosome-forming ability, while the MNase-sensitive non-histone particles are characterized by much lower DNA deformation energy and high nucleosome preference. In addition, we also revealed that remodelers, SNF2 and RSC8, are likely to act in chromatin remodeling by binding to broad nucleosome-depleted regions that are intrinsically favorable for nucleosome positioning. Our data support the important role of position-dependent physical properties of DNA in nucleosome positioning.

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Measuring DNA mechanics on the genome scale

Cited by 14 publications

References 37 publications

Deciphering the mechanical code of genome and epigenome

Deciphering the mechanical code of genome and epigenome

Genome information processing by the INO80 chromatin remodeler positions nucleosomes

A deformation energy model reveals sequence-dependent property of nucleosome positioning

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