scholarly journals Genome information processing by the INO80 chromatin remodeler positions nucleosomes

2020 ◽  
Author(s):  
Elisa Oberbeckmann ◽  
Nils Krietenstein ◽  
Vanessa Niebauer ◽  
Yingfei Wang ◽  
Kevin Schall ◽  
...  
Keyword(s):  
Information Processing ◽  
Nucleosome Positioning ◽  
Yeast Genome ◽  
Sequence Motifs ◽  
Chromatin Remodelers ◽  
Molecular Determinants ◽  
Dna Shape ◽  
Genome Information ◽  
Eukaryotic Genomes ◽  
Active Organization

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.

scholarly journals Genome information processing by the INO80 chromatin remodeler positions nucleosomes

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Elisa Oberbeckmann ◽  
Nils Krietenstein ◽  
Vanessa Niebauer ◽  
Yingfei Wang ◽  
Kevin Schall ◽  
...  
Keyword(s):  
Information Processing ◽  
Nucleosome Positioning ◽  
Yeast Genome ◽  
Sequence Motifs ◽  
Chromatin Remodelers ◽  
Molecular Determinants ◽  
Dna Shape ◽  
Genome Information ◽  
Eukaryotic Genomes ◽  
Active Organization

AbstractThe 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.

scholarly journals Chromatin remodeler Ino80C acts independently of H2A.Z to evict promoter nucleosomes and stimulate transcription of highly expressed genes in yeast

2020 ◽  
Vol 48 (15) ◽  
pp. 8408-8430 ◽  
Author(s):  
Hongfang Qiu ◽  
Emily Biernat ◽  
Chhabi K Govind ◽  
Yashpal Rawal ◽  
Răzvan V Chereji ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Transcriptional Activation ◽  
Histone Variant ◽  
Yeast Genome ◽  
Chromatin Remodeler ◽  
Chromatin Remodelers ◽  
Highly Expressed Genes ◽  
Induced Genes ◽  
Yeast Genes

Abstract The chromatin remodelers SWI/SNF and RSC function in evicting promoter nucleosomes at highly expressed yeast genes, particularly those activated by transcription factor Gcn4. Ino80 remodeling complex (Ino80C) can establish nucleosome-depleted regions (NDRs) in reconstituted chromatin, and was implicated in removing histone variant H2A.Z from the −1 and +1 nucleosomes flanking NDRs; however, Ino80C’s function in transcriptional activation in vivo is not well understood. Analyzing the cohort of Gcn4-induced genes in ino80Δ mutants has uncovered a role for Ino80C on par with SWI/SNF in evicting promoter nucleosomes and transcriptional activation. Compared to SWI/SNF, Ino80C generally functions over a wider region, spanning the −1 and +1 nucleosomes, NDR and proximal genic nucleosomes, at genes highly dependent on its function. Defects in nucleosome eviction in ino80Δ cells are frequently accompanied by reduced promoter occupancies of TBP, and diminished transcription; and Ino80 is enriched at genes requiring its remodeler activity. Importantly, nuclear depletion of Ino80 impairs promoter nucleosome eviction even in a mutant lacking H2A.Z. Thus, Ino80C acts widely in the yeast genome together with RSC and SWI/SNF in evicting promoter nucleosomes and enhancing transcription, all in a manner at least partly independent of H2A.Z editing.

scholarly journals Effect of Sequence-Directed Nucleosome Disruption on Cell-Type-Specific Repression by α2/Mcm1 in the Yeast Genome

2006 ◽  
Vol 5 (11) ◽  
pp. 1925-1933 ◽  
Author(s):  
Nobuyuki Morohashi ◽  
Yuichi Yamamoto ◽  
Shunsuke Kuwana ◽  
Wataru Morita ◽  
Heisaburo Shindo ◽  
...  
Keyword(s):  
Dna Sequences ◽  
Nucleosome Positioning ◽  
Yeast Genome ◽  
Specific Gene ◽  
Cell Type ◽  
Chromatin Structural ◽  
A Cell ◽  
Cell Type Specific ◽  
Acting In Concert ◽  
Modest Effect

ABSTRACT In Saccharomyces cerevisiae, a-cell-specific genes are repressed in MATα cells by α2/Mcm1, acting in concert with the Ssn6-Tup1 corepressors and the Isw2 chromatin remodeling complex, and nucleosome positioning has been proposed as one mechanism of repression. However, prior studies showed that nucleosome positioning is not essential for repression by α2/Mcm1 in artificial reporter plasmids, and the importance of the nucleosome positioning remains questionable. We have tested the function of positioned nucleosomes through alteration of genomic chromatin at the a-cell-specific gene BAR1. We report here that a positioned nucleosome in the BAR1 promoter is disrupted in cis by the insertion of diverse DNA sequences such as poly(dA) · poly(dT) and poly(dC-dG) · poly(dC-dG), leading to inappropriate partial derepression of BAR1. Also, we show that isw2 mutation causes loss of nucleosome positioning in BAR1 in MATα cells as well as partial disruption of repression. Thus, nucleosome positioning is required for full repression, but loss of nucleosome positioning is not sufficient to relieve repression completely. Even though disruption of nucleosome positioning by the cis- and trans-acting modulators of chromatin has a modest effect on the level of transcription, it causes significant degradation of the α-mating pheromone in MATα cells, thereby affecting its cell type identity. Our results illustrate a useful paradigm for analysis of chromatin structural effects at genomic loci.

scholarly journals The dynamic three-dimensional organization of the diploid yeast genome

2016 ◽  
Author(s):  
Seungsoo Kim ◽  
Ivan Liachko ◽  
Donna G Brickner ◽  
Kate Cook ◽  
William S Noble ◽  
...  
Keyword(s):  
Nuclear Periphery ◽  
Three Dimensional ◽  
Culture Conditions ◽  
Yeast Genome ◽  
Nuclear Pore ◽  
Nuclear Pore Complexes ◽  
Chromosome Conformation ◽  
Homolog Pairing ◽  
Pore Complexes ◽  
Eukaryotic Genomes

AbstractThe budding yeast Saccharomyces cerevisiae is a long-standing model for the three-dimensional organization of eukaryotic genomes. Even in this well-studied model, it is unclear how homolog pairing in diploids and environment-induced gene relocalization influence overall genome organization. Here, we performed high-throughput chromosome conformation capture on diverged Saccharomyces hybrid diploids to obtain the first global view of chromosome conformation in diploid yeasts. After controlling for the Rabl-like orientation, we observe significant homolog proximity that increased in saturated culture conditions. Surprisingly, we observe a localized increase in homologous interactions between the HAS1 alleles specifically under galactose induction and saturated growth, mediated by association with nuclear pore complexes at the nuclear periphery. Together, these results reveal that the diploid yeast genome has a dynamic and complex 3D organization.

scholarly journals Dynamic regulation of transcription factors by nucleosome remodeling

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Ming Li ◽  
Arjan Hada ◽  
Payel Sen ◽  
Lola Olufemi ◽  
Michael A Hall ◽  
...  
Keyword(s):  
Direct Evidence ◽  
Nucleosome Positioning ◽  
Regulation Of Transcription ◽  
Dynamic Regulation ◽  
Major Barrier ◽  
Nucleosome Remodeling ◽  
Chromatin Remodelers ◽  
Promoter Architecture ◽  
Sequence Elements ◽  
Dna Template

The chromatin landscape and promoter architecture are dominated by the interplay of nucleosome and transcription factor (TF) binding to crucial DNA sequence elements. However, it remains unclear whether nucleosomes mobilized by chromatin remodelers can influence TFs that are already present on the DNA template. In this study, we investigated the interplay between nucleosome remodeling, by either yeast ISW1a or SWI/SNF, and a bound TF. We found that a TF serves as a major barrier to ISW1a remodeling, and acts as a boundary for nucleosome repositioning. In contrast, SWI/SNF was able to slide a nucleosome past a TF, with concurrent eviction of the TF from the DNA, and the TF did not significantly impact the nucleosome positioning. Our results provide direct evidence for a novel mechanism for both nucleosome positioning regulation by bound TFs and TF regulation via dynamic repositioning of nucleosomes.

scholarly journals Yeast Nucleolin Nsr1 Impedes Replication and Elevates Genome Instability at an Actively Transcribed Guanine-Rich G4 DNA-Forming Sequence

Genetics ◽  
2020 ◽  
Vol 216 (4) ◽  
pp. 1023-1037
Author(s):  
Shivani Singh ◽  
Alexandra Berroyer ◽  
Minseon Kim ◽  
Nayun Kim
Keyword(s):  
Dna Binding ◽  
Genome Stability ◽  
Genome Instability ◽  
Functional Characterization ◽  
Yeast Genome ◽  
Sequence Motifs ◽  
G4 Dna ◽  
C Terminus ◽  
Dna Strand

A significant increase in genome instability is associated with the conformational shift of a guanine-run-containing DNA strand into the four-stranded G-quadruplex (G4) DNA. The mechanism underlying the recombination and genome rearrangements following the formation of G4 DNA in vivo has been difficult to elucidate but has become better clarified by the identification and functional characterization of several key G4 DNA-binding proteins. Mammalian nucleolin (NCL) is a highly specific G4 DNA-binding protein with a well-defined role in the transcriptional regulation of genes with associated G4 DNA-forming sequence motifs at their promoters. The consequence of the in vivo interaction between G4 DNA and nucleolin in respect to the genome instability has not been previously investigated. We show here that the yeast nucleolin Nsr1 is enriched at a G4 DNA-forming sequence in vivo and is a major factor in inducing the genome instability associated with the cotranscriptionally formed G4 DNA in the yeast genome. We also show that Nsr1 results in impeding replication past such a G4 DNA-forming sequence. The G4-associated genome instability and the G4 DNA-binding in vivo require the arginine-glycine-glycine (RGG) repeats located at the C-terminus of the Nsr1 protein. Nsr1 with the deletion of RGG domain supports normal cell growth and is sufficient for its pre-rRNA processing function. However, the truncation of the RGG domain of Nsr1 significantly weakens its interaction with G4 DNA in vivo and restores unhindered replication, overall resulting in a sharp reduction in the genome instability associated with a guanine-rich G4 DNA-forming sequence. Our data suggest that the interaction between Nsr1 with the intact RGG repeats and G4 DNA impairs genome stability by precluding the access of G4-resolving proteins and impeding replication.

scholarly journals Coupling between Sequence-Mediated Nucleosome Organization and Genome Evolution

Genes ◽  
2021 ◽  
Vol 12 (6) ◽  
pp. 851
Author(s):  
Jérémy Barbier ◽  
Cédric Vaillant ◽  
Jean-Nicolas Volff ◽  
Frédéric G. Brunet ◽  
Benjamin Audit
Keyword(s):  
Dna Sequence ◽  
Evolutionary Dynamics ◽  
Mutual Influence ◽  
Nucleosome Positioning ◽  
Sequence Evolution ◽  
Sequence Motifs ◽  
Dna Damage And Repair ◽  
Repair Mechanisms ◽  
Cell Processes

The nucleosome is a major modulator of DNA accessibility to other cellular factors. Nucleosome positioning has a critical importance in regulating cell processes such as transcription, replication, recombination or DNA repair. The DNA sequence has an influence on the position of nucleosomes on genomes, although other factors are also implicated, such as ATP-dependent remodelers or competition of the nucleosome with DNA binding proteins. Different sequence motifs can promote or inhibit the nucleosome formation, thus influencing the accessibility to the DNA. Sequence-encoded nucleosome positioning having functional consequences on cell processes can then be selected or counter-selected during evolution. We review the interplay between sequence evolution and nucleosome positioning evolution. We first focus on the different ways to encode nucleosome positions in the DNA sequence, and to which extent these mechanisms are responsible of genome-wide nucleosome positioning in vivo. Then, we discuss the findings about selection of sequences for their nucleosomal properties. Finally, we illustrate how the nucleosome can directly influence sequence evolution through its interactions with DNA damage and repair mechanisms. This review aims to provide an overview of the mutual influence of sequence evolution and nucleosome positioning evolution, possibly leading to complex evolutionary dynamics.

Gene Regulation in and out of Equilibrium

2020 ◽  
Vol 49 (1) ◽  
pp. 199-226 ◽  
Author(s):  
Felix Wong ◽  
Jeremy Gunawardena
Keyword(s):  
Gene Regulation ◽  
Information Processing ◽  
Thermodynamic Equilibrium ◽  
Fundamental Limits ◽  
Linear Framework ◽  
Biophysical Studies ◽  
Genetic Information Processing ◽  
Gene Regulatory ◽  
Regulatory Properties ◽  
Eukaryotic Genomes

Determining whether and how a gene is transcribed are two of the central processes of life. The conceptual basis for understanding such gene regulation arose from pioneering biophysical studies in eubacteria. However, eukaryotic genomes exhibit vastly greater complexity, which raises questions not addressed by this bacterial paradigm. First, how is information integrated from many widely separated binding sites to determine how a gene is transcribed? Second, does the presence of multiple energy-expending mechanisms, which are absent from eubacterial genomes, indicate that eukaryotes are capable of improved forms of genetic information processing? An updated biophysical foundation is needed to answer such questions. We describe the linear framework, a graph-based approach to Markov processes, and show that it can accommodate many previous studies in the field. Under the assumption of thermodynamic equilibrium, we introduce a language of higher-order cooperativities and show how it can rigorously quantify gene regulatory properties suggested by experiment. We point out that fundamental limits to information processing arise at thermodynamic equilibrium and can only be bypassed through energy expenditure. Finally, we outline some of the mathematical challenges that must be overcome to construct an improved biophysical understanding of gene regulation.

scholarly journals Archaeal Nucleosome Positioning by CTG Repeats

1999 ◽  
Vol 181 (3) ◽  
pp. 1035-1038 ◽  
Author(s):  
Kathleen Sandman ◽  
John N. Reeve
Keyword(s):  
Dna Binding ◽  
Dna Sequences ◽  
Binding Sites ◽  
Shape Recognition ◽  
Nucleosome Positioning ◽  
Dna Binding Proteins ◽  
Ctg Repeats ◽  
Dna Shape ◽  
Ctg Repeat

ABSTRACT DNA shape recognition determines the preferred binding sites for sequence-independent DNA binding proteins, and here we document that archaeal histones assemble archaeal nucleosomes in vitro centered preferentially within (CTG)6 and (CTG)8repeats, close to junctions with flanking mixed-sequence DNA. Archaeal nucleosomes were not positioned by (CTG)4-, (CTG)5-, or (CTG)3AA(CTG)3-containing DNA sequences. The features of CTG repeat-containing sequences that direct eucaryal nucleosome positioning may also be similarly recognized by archaeal histones.

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