A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome

Zhang, Zhenhai; Wippo, Christian J.; Wal, Megha; Ward, E. Sally; Korber, Philipp; Pugh, B. Franklin

doi:10.1126/science.1200508

Cited by 305 publications

(461 citation statements)

References 27 publications

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“…This research has provided insight into the importance of nucleosomal sequence preferences for chromatin organization (7), and has allowed for the creation, refinement, and testing of many models for predicting nucleosome positioning along genomes (8,9). The intrinsic nucleosome-DNA affinity of genomic sequences appears to play a significant role in vivo in positioning nucleosomes in certain regions of the genome, such as transcription start sites (TSSs) and origins of replication (7), alongside other effects like the presence of proteins that compete for the same DNA stretch or the action of chromatin remodelers (10,11).…”

Section: Introductionmentioning

confidence: 99%

“…Most of these studies were conducted in vivo, and therefore do not allow for isolation of effects encoded into the genomic sequences. This body of research shows, however, that sequence effects alone are not generally sufficient to explain in vivo observations (11). An important role is also played by the active regulation of transcription.…”

Section: Introductionmentioning

confidence: 99%

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Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Tompitak

Vaillant

Schiessel

2017

Biophysical Journal

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Sequences that influence nucleosome positioning in promoter regions, and their relation to gene regulation, have been the topic of much research over the last decade. In yeast, significant nucleosome-depleted regions are found, which facilitate transcription. With the arrival of nucleosome positioning maps for the human genome, it was discovered that in our genome, unlike in that of yeast, promoters encode for high nucleosome occupancy. In this work, we look at the genomes of a range of different organisms, to provide a catalog of nucleosome positioning signals in promoters across the tree of life. We utilize a computational model of the nucleosome, based on crystallographic analyses of the structure and elasticity of the nucleosome, to predict the nucleosome positioning signals in promoter regions. To be able to apply our model to large genomic datasets, we introduce an approximative scheme that makes use of the limited range of correlations in nucleosomal sequence preferences to create a computationally efficient approximation of the full biophysical model. Our predictions show that a clear distinction between unicellular and multicellular life is visible in the intrinsically encoded nucleosome affinity. Furthermore, the strength of the nucleosome positioning signals correlates with the complexity of the organism. We conclude that encoding for high nucleosome occupancy, as in the human genome, is in fact a universal feature of multicellular life.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Tompitak

Vaillant

Schiessel

2017

Biophysical Journal

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“…More specifically, the isw2 and isw1 complexes contribute to the positioning of nucleosomes in intergenic regions or in the middle of genes, respectively, which suppresses cryptic, antisense transcription that would otherwise pose a risk of interfering with sense transcription (Whitehouse et al 2007;Tirosh et al 2010). The positioning and phasing of nucleosomes around transcription start sites in yeast, which frequently carry information in the form of histone variants and specific modifications, are brought about by the RSC complex in S. cerevisiae Zhang et al 2011). In fission yeast the CHDtype remodeler, Mit1, has been shown to be involved in aligning nucleosomal arrays with respect to promoter boundaries, a process termed nucleosome "phasing" (Lantermann et al 2010).…”

Section: Nucleosome Remodeling In Chromatin Assembly and Organizationmentioning

confidence: 99%

Nucleosome Remodeling and Epigenetics

Becker

Workman

2013

Cold Spring Harbor Perspectives in Biology

272

203

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“…Nucleosome mapping in situ combined with biochemical studies has revealed that nucleosome positions determine access to DNA regulatory sequences essential to these processes (1,2). Nucleosome position is determined chiefly by DNA sequence and ATP-dependent chromatin remodeling factors (3)(4)(5). The nucleosome includes a linker DNA of variable length and a nucleosome core containing a histone octamer and 147 bp of DNA (6).…”

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confidence: 99%

X-ray structure of the MMTV-A nucleosome core

Frouws

Duda

Richmond

2016

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

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The conformation of DNA bound in nucleosomes depends on the DNA sequence. Questions such as how nucleosomes are positioned and how they potentially bind sequence-dependent nuclear factors require near-atomic resolution structures of the nucleosome core containing different DNA sequences; despite this, only the DNA for two similar α-satellite sequences and a sequence (601) selected in vitro have been visualized bound in the nucleosome core. Here we report the 2.6-Å resolution X-ray structure of a nucleosome core particle containing the DNA sequence of nucleosome A of the 3′-LTR of the mouse mammary tumor virus (147 bp MMTV-A). To our knowledge, this is the first nucleosome core particle structure containing a promoter sequence and crystallized from Mg 2+ ions. It reveals sequence-dependent DNA conformations not seen previously, including kinking into the DNA major groove.chromatin | nucleosome | DNA | X-ray structure | MMTV D NA in eukaryotic cells is wrapped repeatedly in nucleosomes to form chromatin, the substrate engaged by the nuclear machinery to carry out repair, replication, recombination, and transcription of genomes. Nucleosome mapping in situ combined with biochemical studies has revealed that nucleosome positions determine access to DNA regulatory sequences essential to these processes (1, 2). Nucleosome position is determined chiefly by DNA sequence and ATP-dependent chromatin remodeling factors (3-5). The nucleosome includes a linker DNA of variable length and a nucleosome core containing a histone octamer and 147 bp of DNA (6). Many high-resolution structures of nucleosome cores with differing DNA sequences are required to see how the details of DNA conformation could affect nucleosome positioning and dynamics, as well as nuclear factor binding. The DNA studied would most interestingly represent natural sequences of transcription promoters and enhancer elements.Our knowledge of sequence-dependent structure of DNA bound in the nucleosome core relative to the amount of DNA bound in genomes is extremely limited. A resolution of at least 2.6 Å is necessary to evaluate differences in DNA conformations and assess solvent interactions adequately. To date, this highly reliable "library" of DNA structural information pertinent to the nucleosome core consists primarily of two similar sequences of half α-satellite repeats and half the artificially "evolved" sequence 601 (7-10). Further investigations have been limited to substitution of short sequence elements in one of the α-satellite sequences (11, 12). These high-resolution structures have hinged on using palindromic sequences to avoid twofold averaging imposed by crystal packing. The lack of twofold symmetry in the full 601 sequence, for example, resulted in superposition of the electron density of the two different half-sequences (9).We describe here the X-ray structure of a nucleosome core particle (NCP) containing a DNA sequence from mouse mammary tumor virus (MMTV) determined at 2.6 Å resolution. To our knowledge, this is the first NCP structure conta...

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A Packing Mechanism for Nucleosome Organization Reconstituted Across a Eukaryotic Genome

Cited by 305 publications

References 27 publications

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Genomes of Multicellular Organisms Have Evolved to Attract Nucleosomes to Promoter Regions

Nucleosome Remodeling and Epigenetics

X-ray structure of the MMTV-A nucleosome core

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