Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT

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

doi:10.1126/science.abp9466

Cited by 76 publications

(78 citation statements)

References 93 publications

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“…While the nucleosome represents the major histone-DNA assembly in cellular chromatin, histone-DNA complexes with alternative stoichiometries, such as subnucleosomes, have also been observed ( 5 , 6 ). For example, the hexasome, which has one less H2A-H2B dimer than the canonical nucleosome, can form when the transcription machinery traverses a nucleosome during elongation ( 7 , 8 ). Indeed, hexasomes are detected throughout the genome ( 9 , 10 ).…”

mentioning

confidence: 99%

Cryo–electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B

Nozawa

Takizawa

Pierrakeas

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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The canonical nucleosome, which represents the major packaging unit of eukaryotic chromatin, has an octameric core composed of two histone H2A-H2B and H3-H4 dimers with ∼147 base pairs (bp) of DNA wrapped around it. Non-nucleosomal particles with alternative histone stoichiometries and DNA wrapping configurations have been found, and they could profoundly influence genome architecture and function. Using cryo–electron microscopy, we solved the structure of the H3-H4 octasome, a nucleosome-like particle with a di-tetrameric core consisting exclusively of the H3 and H4 histones. The core is wrapped by ∼120 bp of DNA in 1.5 negative superhelical turns, forming two stacked disks that are connected by a H4-H4’ four-helix bundle. Three conformations corresponding to alternative interdisk angles were observed, indicating the flexibility of the H3-H4 octasome structure. In vivo crosslinking experiments detected histone–histone interactions consistent with the H3-H4 octasome model, suggesting that H3-H4 octasomes or related structural features exist in cells.

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mentioning

confidence: 99%

Cryo–electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B

Nozawa

Takizawa

Pierrakeas

et al. 2022

Proc. Natl. Acad. Sci. U.S.A.

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“…Spt4/5 (DSIF for mammals) is one of the transcription elongation factors that is tightly associated with transcribing RNAPII 39 , 40 . It binds and seals the RNAPII DNA-binding cleft 41 , and enhances the transcription elongation efficiency in the nucleosome 35 , 41 – 43 . Interestingly, when the Spt4/5-bound RNAPII structure was superimposed on the current RNAPII-chromatosome complex, Spt4/5 overlapped with the exit linker DNA in the form I complex (Fig.…”

Section: Resultsmentioning

confidence: 99%

Structural basis of RNA polymerase II transcription on the chromatosome containing linker histone H1

et al. 2022

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In chromatin, linker histone H1 binds to nucleosomes, forming chromatosomes, and changes the transcription status. However, the mechanism by which RNA polymerase II (RNAPII) transcribes the DNA in the chromatosome has remained enigmatic. Here we report the cryo-electron microscopy (cryo-EM) structures of transcribing RNAPII-chromatosome complexes (forms I and II), in which RNAPII is paused at the entry linker DNA region of the chromatosome due to H1 binding. In the form I complex, the H1 bound to the nucleosome restricts the linker DNA orientation, and the exit linker DNA is captured by the RNAPII DNA binding cleft. In the form II complex, the RNAPII progresses a few bases ahead by releasing the exit linker DNA from the RNAPII cleft, and directly clashes with the H1 bound to the nucleosome. The transcription elongation factor Spt4/5 masks the RNAPII DNA binding region, and drastically reduces the H1-mediated RNAPII pausing.

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“…A recent structure of the yeast RNAP2 elongation complex revealed that the Spn1 TND preceded by HEAT subdomain is recruited to RNAP2 through association with the Spt5 NGN and KOW2 domains using an interface distinct from the one needed for association with TIMs, leaving the TIM binding site open for interaction with Spt6 [ 49 ]. Importantly, the IWS1-TND:SPT6-TIM interaction interface in the context of fully assembled elongation complexes and RNAP2 is structurally similar to the binary complex resolved by protein NMR or crystallography [ 6 , 21 , 22 , 49 ], confirming that the binary TND:TIM interactions exist in the context of larger assembled complexes.…”

Section: Transcriptional Roles Of Tnd Across Proteins and Speciesmentioning

confidence: 99%

The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder

Čermáková

Veverka

Hodges

2023

Biochemical Society Transactions

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Interaction scaffolds that selectively recognize disordered protein strongly shape protein interactomes. An important scaffold of this type that contributes to transcription is the TFIIS N-terminal domain (TND). The TND is a five-helical bundle that has no known enzymatic activity, but instead selectively reads intrinsically disordered sequences of other proteins. Here, we review the structural and functional properties of TNDs and their cognate disordered ligands known as TND-interacting motifs (TIMs). TNDs or TIMs are found in prominent members of the transcription machinery, including TFIIS, super elongation complex, SWI/SNF, Mediator, IWS1, SPT6, PP1-PNUTS phosphatase, elongin, H3K36me3 readers, the transcription factor MYC, and others. We also review how the TND interactome contributes to the regulation of transcription. Because the TND is the most significantly enriched fold among transcription elongation regulators, TND- and TIM-driven interactions have widespread roles in the regulation of many transcriptional processes.

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Structural basis of nucleosome disassembly and reassembly by RNAPII elongation complex with FACT

Cited by 76 publications

References 93 publications

Cryo–electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B

Cryo–electron microscopy structure of the H3-H4 octasome: A nucleosome-like particle without histones H2A and H2B

Structural basis of RNA polymerase II transcription on the chromatosome containing linker histone H1

The TFIIS N-terminal domain (TND): a transcription assembly module at the interface of order and disorder

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