Structural basis of the nucleosome transition during RNA polymerase II passage

Kujirai, Tomoya; Ehara, Haruhiko; Fujino, Y.; Shirouzu, Mikako; Sekine, S.; Kurumizaka, Hitoshi

doi:10.1126/science.aau9904

Cited by 164 publications

(174 citation statements)

References 47 publications

(32 reference statements)

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“…Compared to transcription on protein‐free templates, chromatin blocked ~80% of TECs from generating full‐length transcripts, and the blocked TECs often arrested or paused for extended periods at multiple positions. The inhibition of transcription elongation observed for archaeal components almost exactly matches the impediment observed of Pol II transcribing through a well‐positioned nucleosome (Xie and Reeve, ; Kireeva et al ., ; Kim et al ., ; Luse et al ., ; Bintu et al ., ; Nock et al ., ; Kwak and Lis, ; Ishibashi et al ., ; Lee and Blobel, ; Studitsky et al ., ; Crickard et al ., ; Van Oss et al ., ; Xu et al ., ; Kujirai et al ., ). The initial collision results in the greatest obstacle, and when the TEC escapes this initial collision, transcription pauses every ~10–15 bp while the TEC traverses the histone complex.…”

Section: Resultsmentioning

confidence: 97%

“…While eukaryotic genomes encode a wealth of factors to both perturb and strengthen the interactions of histones with DNA, the main barrier to the expression of genes is the core histone fold and its interactions with DNA (Chang and Luse, 1997;Kireeva et al, 2005;Kim et al, 2010;Luse et al, 2011;Bintu et al, 2012;Nock et al, 2012;Kwak and Lis, 2013;Studitsky et al, 2016;Lee and Blobel, 2016;Van Oss et al, 2017;Kujirai et al, 2018). No histone modification machinery has been identified in Archaea, nor has evidence of post-translational modification of archaeal histones emerged (Peeters et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

“…The superhelically wrapped DNA shares the geometry, diameter, pitch, and writhe of the eukaryotic nucleosomal superhelix, and specific protein-DNA contacts that stabilize archaeal chromatin are conserved in eukaryotes (Luger et al, 1997;Mattiroli et al, 2017;Bhattacharyya et al, 2018). The eukaryotic nuclear RNA polymerases (RNAPs) and the archaeal RNAP thus regularly encounter -and must overcome -nearly identical histone-based barriers to transcription elongation (Kireeva et al, 2005;Teves et al, 2014;Ehara et al, 2017;Mattiroli et al, 2017;Kujirai et al, 2018).…”

Section: Introductionmentioning

confidence: 99%

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TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

Sanders

Lammers

Marshall

et al. 2019

Molecular Microbiology

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Summary RNA polymerase must surmount translocation barriers for continued transcription. In Eukarya and most Archaea, DNA‐bound histone proteins represent the most common and troublesome barrier to transcription elongation. Eukaryotes encode a plethora of chromatin‐remodeling complexes, histone‐modification enzymes and transcription elongation factors to aid transcription through nucleosomes, while archaea seemingly lack machinery to remodel/modify histone‐based chromatin and thus must rely on elongation factors to accelerate transcription through chromatin‐barriers. TFS (TFIIS in Eukarya) and the Spt4–Spt5 complex are universally encoded in archaeal genomes, and here we demonstrate that both elongation factors, via different mechanisms, can accelerate transcription through archaeal histone‐based chromatin. Histone proteins in Thermococcus kodakarensis are sufficiently abundant to completely wrap all genomic DNA, resulting in a consistent protein barrier to transcription elongation. TFS‐enhanced cleavage of RNAs in backtracked transcription complexes reactivates stalled RNAPs and dramatically accelerates transcription through histone‐barriers, while Spt4–Spt5 changes to clamp‐domain dynamics play a lesser‐role in stabilizing transcription. Repeated attempts to delete TFS, Spt4 and Spt5 from the T. kodakarensis genome were not successful, and the essentiality of both conserved transcription elongation factors suggests that both conserved elongation factors play important roles in transcription regulation in vivo, including mechanisms to accelerate transcription through downstream protein barriers.

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Section: Resultsmentioning

confidence: 97%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

Sanders

Lammers

Marshall

et al. 2019

Molecular Microbiology

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“…A vector containing the Widom 601 sequence was used as a template for PCR. Super-helical locations are assigned based on previous publications (Farnung et al, 2018(Farnung et al, , 2017Kujirai et al, 2018;Sundaramoorthy et al, 2018), assuming potential direction of transcription from negative to positive SHLs. Large-scale PCR reactions were performed with two PCR primers (forward primer: TGT TGG ATG TTT TAT AAT TGA GTG GGT TCC TGT TAT TCC TAG TAA TCA ATC AGT GCC TAT CGA TGT ATA TAT CTG ACA CGT GCC T, reverse primer: CCC CAT CAG AAT CCC GGT GCC G) at a scale of 25 mL.…”

Section: Methodsmentioning

confidence: 99%

Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Farnung

Ochmann

Cramer

2019

Preprint

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The chromatin remodelling enzyme CHD4 is a component of the NuRD and ChAHP complexes that are involved in gene repression. Here we report the cryo-electron microscopy (cryo-EM) structure of Homo sapiens CHD4 engaged with a nucleosome core particle in the presence of the non-hydrolysable ATP analogue AMP-PNP at an overall resolution of 3.1 Å. The ATPase motor of CHD4 binds and distorts nucleosomal DNA at superhelical location (SHL) +2, supporting the 'twist defect' model of chromatin remodelling. CHD4 does not induce unwrapping of terminal DNA, in contrast to its homologue Chd1, which functions in gene activation. Our results also rationalize the effect of CHD4 mutations that are associated with cancer or the intellectual disability disorder Sifrim-Hitz-Weiss syndrome.

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“…hexasome (13)). For example, during transcription, nucleosomes must at least be repositioned (14). Consequently, structural conflicts between neighboring nucleosomes may result in partial histone dissociation, manifesting in vitro as overlapping dinucleosomes (15).…”

Section: Introductionmentioning

confidence: 99%

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

Kameda

Awazu

Togashi

2019

Preprint

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Nucleosomes are structural units of the chromosome consisting of DNA wrapped around histone proteins, and play important roles in compaction and regulation of the chromatin structure. While the structure and dynamics of canonical nucleosomes have been studied extensively, those of nucleosomes in intermediate states, that occur when their structure or positioning is modulated, have been less understood. In particular, the dynamic features of partially disassembled nucleosomes have not been discussed in previous studies. Using all-atom molecular dynamics simulations, in this study, we investigated the dynamics and stability of nucleosome structures lacking a histone-dimer. DNA in nucleosomes lacking a histone H2A/H2B dimer was drastically deformed due to loss of local interactions between DNA and histones. In contrast, conformation of DNA in nucleosomes lacking H3/H4 was similar to the canonical nucleosome, as the H2A C-terminal domain infiltrated the space originally occupied by the dissociated H3/H4 histones and stabilized DNA in close proximity. Our results suggest that, besides histone chaperones, the intrinsic dynamics of nucleosomes support the exchange of H2A/H2B, which is significantly more frequent than that of H3/H4. Statement of SignificanceEukaryotic chromosomes are composed of nucleosomes, in which the DNA wraps around the core histone proteins. To enable transcription and replication of DNA, or to modulate these functions by exchange of histones, nucleosomes should be at least partially disassembled, as evidenced by the observation of nucleosome structures lacking an H2A/H2B histone dimer by crystallography. The dynamic behavior of nucleosomes in such intermediate states may affect gene expression and repair, however it has not been completely elucidated so far. In this study, we adopted molecular dynamics simulations to analyze the conformational changes in partially disassembled nucleosomes. Enhanced structural fluctuations of DNA were observed in these nucleosomes, which may, as well as specific histone chaperones, support the exchange of H2A/H2B.

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Structural basis of the nucleosome transition during RNA polymerase II passage

Cited by 164 publications

References 47 publications

TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

TFS and Spt4/5 accelerate transcription through archaeal histone‐based chromatin

Nucleosome-CHD4 chromatin remodeller structure explains human disease mutations

Histone Tail Dynamics in Partially Disassembled Nucleosomes During Chromatin Remodeling

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