Functional interplay between Mediator and RSC chromatin remodeling complex controls nucleosome-depleted region maintenance at promoters

André, Kévin M.; Aiach, Nathalie Giordanengo; Martinez-Fernandez, Veronica; Zeitler, Leo; Alberti, Adriana; Goldar, Arach; Werner, Michel; Wilkes, Cyril Denby; Soutourina, Julie

doi:10.1016/j.celrep.2023.112465

Cited by 7 publications

(6 citation statements)

References 45 publications

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“…This means that fragments shorter than 130 bp and longer than 200 bp were removed from analysis. Mediator and Sth1 ChIP-seq were taken from [ 56 ] (ArrayExpress accession number E-MTAB-12198). We used Pol II ChIP-seq from our previous study [ 62 ].…”

Section: Methodsmentioning

confidence: 99%

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A genome-wide comprehensive analysis of nucleosome positioning in yeast

Zeitler,

André,

Alberti

et al. 2024

PLoS Comput Biol

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In eukaryotic cells, the one-dimensional DNA molecules need to be tightly packaged into the spatially constraining nucleus. Folding is achieved on its lowest level by wrapping the DNA around nucleosomes. Their arrangement regulates other nuclear processes, such as transcription and DNA repair. Despite strong efforts to study nucleosome positioning using Next Generation Sequencing (NGS) data, the mechanism of their collective arrangement along the gene body remains poorly understood. Here, we classify nucleosome distributions of protein-coding genes in Saccharomyces cerevisiae according to their profile similarity and analyse their differences using functional Principal Component Analysis. By decomposing the NGS signals into their main descriptive functions, we compared wild type and chromatin remodeler-deficient strains, keeping position-specific details preserved whilst considering the nucleosome arrangement as a whole. A correlation analysis with other genomic properties, such as gene size and length of the upstream Nucleosome Depleted Region (NDR), identified key factors that influence the nucleosome distribution. We reveal that the RSC chromatin remodeler—which is responsible for NDR maintenance—is indispensable for decoupling nucleosome arrangement within the gene from positioning outside, which interfere in rsc8-depleted conditions. Moreover, nucleosome profiles in chd1Δ strains displayed a clear correlation with RNA polymerase II presence, whereas wild type cells did not indicate a noticeable interdependence. We propose that RSC is pivotal for global nucleosome organisation, whilst Chd1 plays a key role for maintaining local arrangement.

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Section: Methodsmentioning

confidence: 99%

“…MNase sequencing reads were taken from [18] and [12] (GEO accession numbers GSE69400 and GSE73428, respectively) and treated as in our previous study [56]. To be precise, reads from Fastq files were trimmed with trim_galore (v0.6.5) [57] and cutadapt (v3.1) [58].…”

Section: Data Treatmentmentioning

confidence: 99%

A genome-wide comprehensive analysis of nucleosome positioning in yeast

Zeitler,

André,

Alberti

et al. 2024

PLoS Comput Biol

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“…Finally, a recent report revealed a physical interaction between RSC and the Mediator complex, working as a co-activator at promoters [61]. Whether Mediator is involved in NDR resetting after replication remains to be investigated.…”

Section: Rsc Atpase Activity As the Initiator Of Promoter Ndr Resetti...mentioning

confidence: 98%

Refined mechanism of promoter Nucleosome-Depleted Regions resetting after replication

Zencir,

Gill,

Stutz

et al. 2024

Preprint

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Replication disrupts chromatin organization. Thus, the rapid resetting of nucleosome positioning is essential to maintain faithful gene expression. The initial step of this reconfiguration occurs at Nucleosome-Depleted Regions (NDRs). While studies have elucidated the role of Transcription Factors (TFs) and Chromatin Remodelers (CRs) in vitro or in maintaining NDRs in vivo, none has addressed their in vivo function shortly after replication. Through purification of nascent chromatin in yeast, we dissected the choreography of events governing the proper positioning of the -1/+1 nucleosomes flanking promoter NDRs. Our findings reveal that CRs are the primary contributors of -1/+1 repositioning post-replication, with RSC acting upstream of INO80. Surprisingly, while Reb1 and Abf1 TFs are not essential for NDR resetting, they are required for NDR maintenance via the promotion of H3 acetylations. Altogether, we propose a two-step model for NDR resetting in S. cerevisiae: first, CRs alone reset promoter NDRs after replication, while a combination of TFs and CRs is required for subsequent maintenance.

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“…One such family of co-activators is SWI/SNF (SWItch/Sucrose Non-Fermentable), that physically interacts with the mediator to establish nucleosome-depleted regions through nucleosome clearing. 37 , 38 SWI/SNF binds to nucleosomal DNA with its translocase domain which is composed of torsion domain and tracking domain. The torsion domain, upon ATP hydrolysis, leads to directional DNA translocation, destroying histone-DNA contacts and creating a transient DNA loop.…”

Section: Mechanism Of Transcriptional Co-activationmentioning

confidence: 99%

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

Talukdar,

Chatterji

2023

Sig Transduct Target Ther

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Specific cell states in metazoans are established by the symphony of gene expression programs that necessitate intricate synergic interactions between transcription factors and the co-activators. Deregulation of these regulatory molecules is associated with cell state transitions, which in turn is accountable for diverse maladies, including developmental disorders, metabolic disorders, and most significantly, cancer. A decade back most transcription factors, the key enablers of disease development, were historically viewed as ‘undruggable’; however, in the intervening years, a wealth of literature validated that they can be targeted indirectly through transcriptional co-activators, their confederates in various physiological and molecular processes. These co-activators, along with transcription factors, have the ability to initiate and modulate transcription of diverse genes necessary for normal physiological functions, whereby, deregulation of such interactions may foster tissue-specific disease phenotype. Hence, it is essential to analyze how these co-activators modulate specific multilateral processes in coordination with other factors. The proposed review attempts to elaborate an in-depth account of the transcription co-activators, their involvement in transcription regulation, and context-specific contributions to pathophysiological conditions. This review also addresses an issue that has not been dealt with in a comprehensive manner and hopes to direct attention towards future research that will encompass patient-friendly therapeutic strategies, where drugs targeting co-activators will have enhanced benefits and reduced side effects. Additional insights into currently available therapeutic interventions and the associated constraints will eventually reveal multitudes of advanced therapeutic targets aiming for disease amelioration and good patient prognosis.

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Functional interplay between Mediator and RSC chromatin remodeling complex controls nucleosome-depleted region maintenance at promoters

Cited by 7 publications

References 45 publications

A genome-wide comprehensive analysis of nucleosome positioning in yeast

A genome-wide comprehensive analysis of nucleosome positioning in yeast

Refined mechanism of promoter Nucleosome-Depleted Regions resetting after replication

Transcriptional co-activators: emerging roles in signaling pathways and potential therapeutic targets for diseases

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