Structure of an H1-Bound 6-Nucleosome Array Reveals an Untwisted Two-Start Chromatin Fiber Conformation

Garcia-Saez, I.; Menoni, Hervé; Boopathi, Ramachandran; Shukla, Manu; Soueidan, Lama; Noirclerc‐Savoye, Marjolaine; Roy, Aline Le; Skoufias, Dimitrios A.; Bednář, Jan; Hamiche, Ali; Angelov, Dimitar; Petosa, Carlo; Dimitrov, Stéfan

doi:10.1016/j.molcel.2018.09.027

Cited by 101 publications

(132 citation statements)

References 82 publications

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“…Our results help support experimental evidence from Cryo‐EM and X‐ray structures suggesting that the off‐dyad binding mode is a better condenser . Importantly, we propose for the first time the structure of chromatosomes containing two LH bound and the best combination of binding modes to achieve highest compaction.…”

Section: Illustrative Studies: Mesoscale Modeling To Help Interpret Esupporting

confidence: 83%

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

Portillo‐Ledesma

Schlick

2019

WIREs Comput Mol Sci

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Chromatin structure, dynamics, and function are being intensely investigated by a variety of methods, including microscopy, X‐ray diffraction, nuclear magnetic resonance, biochemical crosslinking, chromosome conformation capture, and computation. The modeling helps interpret experimental data and generate configurations and mechanisms related to the three‐dimensional organization and function of the genome. Experimental contact maps, in particular, as obtained by a variety of chromosome conformation capture methods, are of increasing interest due to their implications on genome structure and regulation on many levels. In this perspective, using seven examples from our group's studies, we illustrate how molecular modeling can help interpret such experimental data. Specifically, we show how computed contact maps related to experimental systems can help interpret structures of nucleosomes, chromatin higher‐order folding, domain segregation mechanisms, gene organization, and the effect on chromatin structure of external and internal fiber parameters, such as nucleosome positioning, presence of nucleosome free regions, histone post‐translational modifications, and linker histone binding. We argue that such computations on multiple spatial and temporal scales will be increasingly important for the integration of genomic, epigenomic, and biophysical data on chromatin structure and related cellular processes. This article is categorized under: Structure and Mechanism > Computational Biochemistry and Biophysics

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Section: Illustrative Studies: Mesoscale Modeling To Help Interpret Esupporting

confidence: 83%

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

Portillo‐Ledesma

Schlick

2019

WIREs Comput Mol Sci

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“…Chromatin fibers are conformationally heterogeneous, as exemplified by structural studies (Ekundayo et al, 2017;Garcia-Saez et al, 2018;Routh et al, 2008) or crosslinking experiments (Grigoryev et al, 2009). We and others have previously shown that chromatin fiber contacts are highly dynamic (Kilic et al, 2018b;Li et al, 2016;Poirier et al, 2009).…”

Section: Rap1 Passively Alters Local Higher-order Chromatin Structurementioning

confidence: 99%

Chromatin Fiber Invasion and Nucleosome Displacement by the Rap1 Transcription Factor

et al. 2020

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Graphical Abstract Highlights d The yeast transcription factor Rap1 can invade compact chromatin d Rap1 directly opens chromatin structure by preventing nucleosome stacking d Stable Rap1 binding requires collaboration with RSC to shift promoter nucleosomes In Brief Mivelaz et al. use single-molecule fluorescence approaches and highly defined chromatin systems to show that the yeast transcription factor Rap1 can invade compact chromatin fibers and directly open chromatin structure. For stable binding, Rap1 then collaborates with RSC to displace nucleosomes from its binding sites, generating an active promoter state. SUMMARY Pioneer transcription factors (pTFs) bind to target sites within compact chromatin, initiating chromatin remodeling and controlling the recruitment of downstream factors. The mechanisms by which pTFs overcome the chromatin barrier are not well understood.Here, we reveal, using single-molecule fluorescence, how the yeast transcription factor Rap1 invades and remodels chromatin. Using a reconstituted chromatin system replicating yeast promoter architecture, we demonstrate that Rap1 can bind nucleosomal DNA within a chromatin fiber but with shortened dwell times compared to naked DNA. Moreover, we show that Rap1 binding opens chromatin fiber structure by inhibiting inter-nucleosome contacts. Finally, we reveal that Rap1 collaborates with the chromatin remodeler RSC to displace promoter nucleosomes, paving the way for long-lived bound states on newly exposed DNA. Together, our results provide a mechanistic view of how Rap1 gains access and opens chromatin, thereby establishing an active promoter architecture and controlling gene expression.

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“…An important determinant of chromatin folding are the linker histones. In contrast to core histones they are mobile and bind the histone dyad through their globular domain [34] with their long C-terminal tail draped along the chromatin fibre. Under physiological salt conditions linker histones promote folding of the chromatin into folded structures; in this state the compact chromatin sediments rapidly in a sucrose gradient, but if the histones are removed, unfolding the fibre, its sedimentation decreases [35].…”

Section: Can Nuclear Rna Affect Chromatin Folding?mentioning

confidence: 99%

RNA: Nuclear Glue for Folding the Genome

Nozawa

Gilbert

2019

Trends in Cell Biology

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A significant amount of RNA is present in the nucleus of mammalian cells but only a small proportion of it is destined for the cytoplasm and subsequent translation, leaving much RNA to associate with chromatin. Historically nuclear RNA was thought to interact with proteins to form a filamentous nuclear matrix, but this idea became less popular as more dynamic models of chromatin behavior became more prevalent. Using new molecular and imaging approaches it is becoming clear that RNA should be considered as an integral component of nuclear organisation; it is transcriptionally responsive and interacts with abundant nuclear RNA binding proteins. We suggest that these protein/RNA structures form a dynamic nuclear mesh that can regulate interphase chromatin structure.

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Structure of an H1-Bound 6-Nucleosome Array Reveals an Untwisted Two-Start Chromatin Fiber Conformation

Cited by 101 publications

References 82 publications

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

Bridging chromatin structure and function over a range of experimental spatial and temporal scales by molecular modeling

Chromatin Fiber Invasion and Nucleosome Displacement by the Rap1 Transcription Factor

RNA: Nuclear Glue for Folding the Genome

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