Structure of the SWI/SNF complex bound to the nucleosome and insights into the functional modularity

He, Zhenyu; Chen, Kangjing; Ye, Youpi; Chen, Zhucheng

doi:10.1038/s41421-021-00262-5

Cited by 15 publications

(14 citation statements)

References 16 publications

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“…There is good concordance of the CX-MS data with the cryo-EM structure of nucleosome-bound SWI/SNF as seen by the majority of the lysine pairs observed in the intra-and inter-links having a Cα-Cα distance of ≤30 angstroms in the solved structure and are similar to that observed earlier for CX-MS of free SWI/SNF 14 (Figure S3). The Snf2, Snf5, Arp7, Swi1 and Snf6 subunits crosslinked to histones, consistent with the recent cryo-EM structures of nucleosome-bound ySWI/SNF 14,15 (Figure S3a). The histones crosslink the C-lobe, the linker region between the two lobes of the ATPase domain and the HSA domain in full agreement with the cryo-EM structure.…”

Section: Resultssupporting

confidence: 88%

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming

Saha

Hailu

Hada

et al. 2023

Preprint

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The SWI/SNF ATP-dependent chromatin remodeler is a master regulator of the epigenome; controlling pluripotency and differentiation. Towards the C-terminus of the catalytic subunit of SWI/SNF is a motif called the AT-hook that is evolutionary conserved. The AT-hook is present in many chromatin modifiers and generally thought to help anchor them to DNA. We observe the AT-hook however regulates the intrinsic DNA-stimulated ATPase activity without promoting SWI/SNF recruitment to DNA or nucleosomes by increasing the reaction velocity a factor of 13 with no accompanying change in substrate affinity (KM). The changes in ATP hydrolysis causes an equivalent change in nucleosome movement, confirming they are tightly coupled. Attenuation of SWI/SNF remodeling activity by the AT-hook is important in vivo for SWI/SNF regulation of chromatin structure and gene expression in yeast and mouse embryonic stem cells. The AT-hook in SWI/SNF is required for transcription regulation and activation of state-specific enhancers critical in cell lineage priming. Similarly, the AT-hook is required in yeast SWI/SNF for activation of genes involved in amino acid biosynthesis and metabolizing ethanol. Our findings highlight the importance of studying SWI/SNF attenuation versus eliminating the catalytic subunit or completely shutting down its enzymatic activity.

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Section: Resultssupporting

confidence: 88%

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming

Saha

Hailu

Hada

et al. 2023

Preprint

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“…Notably, the C-terminal helix of Ioc3 (referred as to the finger helix) binds to the H2A-H2B acidic patch of the N2 nucleosome, Fig 3d. Four arginine residues, Arg735, Arg738, Arg739 and Arg742 cluster on one side of the finger helix, with similar orientations and compositions to those of the finger helices of the Snf5/Sfh1/SMARCB1 subunits of the SWI/SNF family complexes 40–42 , supporting functional convergence on a common mechanism of nucleosome recognition, Fig. S7.…”

Section: Recognition Of the N2 Nucleosome By Ioc3mentioning

confidence: 76%

Structure of the ISW1a complex bound to the dinucleosome

Chen

Sia

et al. 2023

Preprint

Self Cite

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Nucleosomes are basic repeating units of chromatin, and form regularly spaced arrays in cells. Chromatin remodelers alter the positions of nucleosomes, and are vital in regulating chromatin organization and gene expression. Here we report the cryoEM structure of chromatin remodeler ISW1a complex bound to the dinucleosome. Each subunit of the complex recognizes a different nucleosome. The motor subunit binds to the mobile nucleosome and recognizes the acidic patch through two arginine residues, and the DNA-binding module interacts with the entry DNA at the nucleosome edge. This nucleosome-binding mode provides the structural basis for linker DNA sensing of the motor. Notably, the Ioc3 subunit recognizes the disk face of the adjacent nucleosome through the H4 tail, the acidic patch and the nucleosomal DNA, which is important for the spacing activity in vitro, and for nucleosome organization and cell fitness in vivo. Together, these findings support the nucleosome spacing activity of ISW1a, and add a new mode of nucleosome remodeling in the context of a chromatin environment.

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“…We reasoned that pH i changes could affect the intrinsic nucleosome remodeling activity of SWI/SNF or alternatively might impact the interactions of SWI/SNF with transcription factors. Indeed, recent structural evidence ( He et al, 2021 ) shows that the QLCs of not only SNF5 but also several other SWI/SNF subunits appear to be poised for interaction with transcription factors on DNA immediately downstream of the nucleosome ( Figure 5—figure supplement 1 ). We used a fluorescence-based strategy in vitro to investigate these potential pH-sensing mechanisms.…”

Section: Resultsmentioning

confidence: 97%

“…We reasoned that pH i changes could affect the intrinsic nucleosome remodeling activity of SWI/SNF, or alternatively might impact the interactions of SWI/SNF with transcription factors. Indeed, recent structural evidence (He et al, 2021) shows that the QLCs of not only SNF5, but also several other SWI/SNF subunits appear to be poised for interaction with transcription factors on DNA immediately downstream of the nucleosome (Figure 5 In the absence of SWI/SNF activity, the center-positioned nucleosome has a low FRET signal, but ATP-dependent mobilization of the nucleosome towards the distal DNA end leads to an increase in FRET (Brune et al, 1994;Luger et al, 1999;Sen et al, 2017;Smith and Peterson, 2005;Zhou and Narlikar, 2016) (Figure 5). In the absence of competitor DNA, SWI/SNF does not require an interaction with a transcription factor to be recruited to the mononucleosome and thus intrinsic nucleosome remodeling activity can be assessed independently of recruitment.…”

Section: The Snf5 Qlc Mediates a Ph-sensitive Transcription Factor In...mentioning

confidence: 99%

SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence

Gutierrez

Brittingham

Karadeniz

et al. 2022

eLife

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It is increasingly appreciated that intracellular pH changes are important biological signals. This motivates the elucidation of molecular mechanisms of pH-sensing. We determined that a nucleocytoplasmic pH oscillation was required for the transcriptional response to carbon starvation in Saccharomyces cerevisiae. The SWI/SNF chromatin remodeling complex is a key mediator of this transcriptional response. A glutamine-rich low complexity domain (QLC) in the SNF5 subunit of this complex, and histidines within this sequence, were required for efficient transcriptional reprogramming. Furthermore, the SNF5 QLC mediated pH-dependent recruitment of SWI/SNF to an acidic transcription factor in a reconstituted nucleosome remodeling assay. Simulations showed that protonation of histidines within the SNF5 QLC lead to conformational expansion, providing a potential biophysical mechanism for regulation of these interactions. Together, our results indicate that that pH changes are a second messenger for transcriptional reprogramming during carbon starvation, and that the SNF5 QLC acts as a pH-sensor.

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Structure of the SWI/SNF complex bound to the nucleosome and insights into the functional modularity

Cited by 15 publications

References 16 publications

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming

The AT-hook is an evolutionarily conserved auto-regulatory domain of SWI/SNF required for cell lineage priming

Structure of the ISW1a complex bound to the dinucleosome

SWI/SNF senses carbon starvation with a pH-sensitive low-complexity sequence

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