scholarly journals Emergence of robust nucleosome patterns from an interplay of positioning mechanisms

2018 ◽  
Author(s):  
Johannes Nuebler ◽  
Michael Wolff ◽  
Benedikt Obermayer ◽  
Wolfram Möbius ◽  
Ulrich Gerland
Keyword(s):  
Dna Sequence ◽  
Chromatin Remodeling ◽  
Nucleosome Positioning ◽  
Eukaryotic Cells ◽  
Active Chromatin ◽  
Complex Interplay ◽  
Quantitative Characteristics ◽  
Characteristic Features ◽  
Species Specific ◽  
Effective Description

AbstractProper positioning of nucleosomes in eukaryotic cells is determined by a complex interplay of factors, including nucleosome-nucleosome interactions, DNA sequence, and active chromatin remodeling. Yet, characteristic features of nucleosome positioning, such as gene-averaged nucleosome patterns, are surprisingly robust across perturbations, conditions, and species. Here, we explore how this robustness arises despite the underlying complexity. We leverage mathematical models to show that a large class of positioning mechanisms merely affects the quantitative characteristics of qualitatively robust positioning patterns. We demonstrate how statistical positioning emerges as an effective description from the complex interplay of different positioning mechanisms, which ultimately only renormalize the model parameter quantifying the effective softness of nucleosomes. This renormalization can be species-specific, rationalizing a puzzling discrepancy between the effective nucleosome softness of S. pombe and S. cerevisiae. More generally, we establish a quantitative framework for dissecting the interplay of different nucleosome positioning determinants.

scholarly journals Theory of active chromatin remodeling

2019 ◽  
Author(s):  
Zhongling Jiang ◽  
Bin Zhang
Keyword(s):  
Chromatin Remodeling ◽  
Computational Models ◽  
Energy Landscape ◽  
Nucleosome Positioning ◽  
Active Chromatin ◽  
Intrinsic Signals ◽  
Biologically Relevant ◽  
The Impact ◽  
Prediction In Silico

Nucleosome positioning controls the accessible regions of chromatin and plays essential roles in DNA-templated processes. ATP driven remodeling enzymes are known to be crucial for its establishment in vivo, but their non-equilibrium nature has hindered the development of a unified theoretical framework for nucleosome positioning. Using a perturbation theory, we show that the effect of these enzymes can be well approximated by effective equilibrium models with rescaled temperatures and interactions. Numerical simulations support the accuracy of the theory in predicting both kinetic and steady-state quantities, including the effective temperature and the radial distribution function, in biologically relevant regimes. The energy landscape view emerging from our study provides an intuitive understanding for the impact of remodeling enzymes in either reinforcing or overwriting intrinsic signals for nucleosome positioning, and may help improve the accuracy of computational models for its prediction in silico.

scholarly journals The biogenesis and function of nucleosome arrays

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ashish Kumar Singh ◽  
Tamás Schauer ◽  
Lena Pfaller ◽  
Tobias Straub ◽  
Felix Mueller-Planitz
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Dna Damage ◽  
Dna Sequence ◽  
Chromatin Remodeling ◽  
Genome Engineering ◽  
Genotoxic Stress ◽  
Eukaryotic Cells ◽  
Nucleosome Density ◽  
And Function

AbstractNumerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shape the nucleosome landscape. The precise contributions of these processes remain unclear due to their functional redundancy in vivo. By incisive genome engineering, we radically decreased their redundancy in Saccharomyces cerevisiae. The transcriptional machinery strongly disrupts evenly spaced nucleosomes. Proper nucleosome density and DNA sequence are critical for their biogenesis. The INO80 remodeling complex helps space nucleosomes in vivo and positions the first nucleosome over genes in an H2A.Z-independent fashion. INO80 requires its Arp8 subunit but unexpectedly not the Nhp10 module for spacing. Cells with irregularly spaced nucleosomes suffer from genotoxic stress including DNA damage, recombination and transpositions. We derive a model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.

scholarly journals The biogenesis and function of nucleosome arrays

2021 ◽  
Author(s):  
Ashish Kumar Singh ◽  
Tamás Schauer ◽  
Lena Pfaller ◽  
Tobias Straub ◽  
Felix Mueller-Planitz
Keyword(s):  
Dna Sequence ◽  
Chromatin Remodeling ◽  
Genome Engineering ◽  
Genotoxic Stress ◽  
Eukaryotic Cells ◽  
Complex Spaces ◽  
Nucleosome Density ◽  
Cryptic Transcription ◽  
And Function

AbstractNumerous chromatin remodeling enzymes position nucleosomes in eukaryotic cells. Aside from these factors, transcription, DNA sequence, and statistical positioning of nucleosomes also shapes the nucleosome landscape. Precise contributions of these processes remain unclear due to their functional redundancy in vivo. By incisive genome engineering, we radically decreased their redundancy in Saccharomyces cerevisiae. The transcriptional machinery is strongly disruptive of evenly spaced nucleosomes, and proper nucleosome density and DNA sequence critical for their biogenesis. The INO80 remodeling complex spaces nucleosomes in vivo and positions the first nucleosome over genes in an H2A.Z-independent fashion. INO80 requires its Arp8 subunit but unexpectedly not the Nhp10 module for spacing. Spaced nucleosomes prevent cryptic transcription and protect cells against genotoxic stress such as DNA damage, recombination and transpositions. We derive a unifying model of the biogenesis of the nucleosome landscape and suggest that it evolved not only to regulate but also to protect the genome.

A species-specific satellite DNA from the entomopathogenic nematode Heterorhabditis indicus

Genome ◽  
1998 ◽  
Vol 41 (2) ◽  
pp. 148-153 ◽  
Author(s):  
Monique Abadon ◽  
Eric Grenier ◽  
Christian Laumond ◽  
Pierre Abad
Keyword(s):  
Dna Sequence ◽  
Satellite Dna ◽  
Tandem Repeats ◽  
Sequence Data ◽  
Entomopathogenic Nematode ◽  
Consensus Sequence ◽  
Repeated Sequence ◽  
Nucleotide Sequence Analysis ◽  
Specific Sequence ◽  
Species Specific

An AluI satellite DNA family has been cloned from the entomopathogenic nematode Heterorhabditis indicus. This repeated sequence appears to be an unusually abundant satellite DNA, since it constitutes about 45% of the H. indicus genome. The consensus sequence is 174 nucleotides long and has an A + T content of 56%, with the presence of direct and inverted repeat clusters. DNA sequence data reveal that monomers are quite homogeneous. Such homogeneity suggests that some mechanism is acting to maintain the homogeneity of this satellite DNA, despite its abundance, or that this repeated sequence could have appeared recently in the genome of H. indicus. Hybridization analysis of genomic DNAs from different Heterorhabditis species shows that this satellite DNA sequence is specific to the H. indicus genome. Considering the species specificity and the high copy number of this AluI satellite DNA sequence, it could provide a rapid and powerful tool for identifying H. indicus strains.Key words: AluI repeated DNA, tandem repeats, species-specific sequence, nucleotide sequence analysis.

scholarly journals Osteocalcin Production in Primary Osteoblast Cultures Derived from Normal and Hyp Mice

Endocrinology ◽  
1998 ◽  
Vol 139 (1) ◽  
pp. 35-43 ◽  
Author(s):  
Thomas O. Carpenter ◽  
Kathleen C. Moltz ◽  
Bruce Ellis ◽  
Monica Andreoli ◽  
Thomas L. McCarthy ◽  
...  
Keyword(s):  
Messenger Rna ◽  
Cultured Cells ◽  
Primary Cultures ◽  
Specific Effect ◽  
Continuous Exposure ◽  
Primary Osteoblast ◽  
Characteristic Features ◽  
Species Specific ◽  
Osteocalcin Production

Abstract Rickets and osteomalacia are characteristic features of the Hyp mouse model of human X-linked hypophosphatemia. Hyp mice demonstrate elevated circulating osteocalcin levels, as well as altered regulation of osteocalcin by 1,25(OH)2D3. Whether this osteocalcin abnormality is intrinsic to the osteoblast, or mediated by the in vivo milieu, has not been established. We therefore characterized osteocalcin production and its regulation by 1,25(OH)2D3 in primary cultures of murine osteoblasts and examined osteocalcin and its messenger RNA in response to 1,25(OH)2D3 in cultures of Hyp mouse-derived osteoblasts. Cell viability and osteocalcin production are optimal when murine cells are harvested within 36 h of age. Murine primary osteoblast cultures mineralize and produce osteocalcin in a maturation-dependent fashion (as demonstrated in other species), and continuous exposure to 1,25(OH)2D3, beginning at day 9 of culture, inhibits osteoblast differentiation and osteocalcin production and prevents mineralization of the culture. However, in contrast to other species, exposure to 1,25(OH)2D3, added later (days 17–25) in culture, does not stimulate osteocalcin but arrests osteocalcin production at current levels. Ambient media levels of osteocalcin were no different in cultures from Hyp mice and their normal litter mates, and the down-regulatory response to 1,25(OH)2D3 was comparable in cultures from normal and Hyp mice. Furthermore, expression of osteocalcin messenger RNA in murine cultures is reduced with exposure to 1,25(OH)2D3, and there is no difference between normal and Hyp cultures in this response. Thus, primary murine osteoblasts manifest a species-specific effect of 1,25(OH)2D3 on osteocalcin production. Furthermore, the increased serum osteocalcin production seen in intact Hyp mice, and the altered response to 1,25(OH)2D3 in Hyp mice, are not observed in osteoblast cultures derived from the mutant strain. These data indicate that abnormalities of osteocalcin described in intact Hyp mice require factors other than those present in cultured cells.

scholarly journals Nucleosome Positioning with Set of Key Positions and Nucleosome Affinity

2014 ◽  
Vol 8 (1) ◽  
pp. 166-170 ◽  
Author(s):  
Jia Wang ◽  
Shuai Liu ◽  
Weina Fu
Keyword(s):  
Neural Network ◽  
Experimental Data ◽  
Dna Sequence ◽  
Dna Sequences ◽  
Nucleosome Positioning ◽  
Experimental Results ◽  
Negative Effects ◽  
Sequence Structure ◽  
Precise Positioning ◽  
Histone Octamer

The formation and precise positioning of nucleosome in chromatin occupies a very important role in studying life process. Today, there are many researchers who discovered that the positioning where the location of a DNA sequence fragment wraps around a histone octamer in genome is not random but regular. However, the positioning is closely relevant to the concrete sequence of core DNA. So in this paper, we analyzed the relation between the affinity and sequence structure of core DNA, and extracted the set of key positions. In these positions, the nucleotide sequences probably occupy mainly action in the binding. First, we simplified and formatted the experimental data with the affinity. Then, to find the key positions in the wrapping, we used neural network to analyze the positive and negative effects of nucleosome generation for each position in core DNA sequences. However, we reached a class of weights with every position to describe this effect. Finally, based on the positions with high weights, we analyzed the reason why the chosen positions are key positions, and used these positions to construct a model for nucleosome positioning prediction. Experimental results show the effectiveness of our method.

Sign in / Sign up

Export Citation Format

Share Document