Acute BAF perturbation causes immediate changes in chromatin accessibility

Schick, Sandra; Grosche, Sarah; Kohl, Katharina; Drpic, Danica; Jaeger, Martin G.; Marella, Chakravarthy; Imrichová, Hana; Lin, Jung-Ming G.; Hofstätter, Gerald; Schuster, Michael; Rendeiro, André F.; Koren, Anna; Petronczki, Mark; Bock, Christoph; Müller, André C.; Ciulli, Alessio; Kubicek, Stefan

doi:10.1038/s41588-021-00777-3

Cited by 130 publications

(109 citation statements)

References 64 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…By integrating our live-cell SMT measurements with available genome-wide localization and protein expression data, we estimate temporal occupancies ranging from 11  7.2 to 94  41% for RSC, SWI/SNF, INO80, and ISW2 at target promoter regions including the NDR and flanking nucleosomes. Our findings of highly dynamic and frequent remodeler-nucleosome interactions are consistent with recent genomics studies showing substantial changes in nucleosome positions upon rapid, conditional inactivation of remodelers in yeast and mammalian systems (Iurlaro et al, 2021;Klein-Brill et al, 2019;Kubik et al, 2019;Schick et al, 2021). Accordingly, we envision a nucleosome remodeling cycle at promoters in which remodeler combinations undergo frequent association, ATP-dependent mobilization and dissociation from chromatin to dynamically fine-tune -1 and +1 nucleosome positions (Figure 8).…”

Section: A Temporal Model For Nucleosome Remodeling At Ndrssupporting

confidence: 90%

Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Kim

Visanpattanasin

Jou

et al. 2021

eLife

View full text Add to dashboard Cite

Conserved ATP-dependent chromatin remodelers establish and maintain genome-wide chromatin architectures of regulatory DNA during cellular lifespan, but the temporal interactions between remodelers and chromatin targets have been obscure. We performed live-cell single-molecule tracking for RSC, SWI/SNF, CHD1, ISW1, ISW2, and INO80 remodeling complexes in budding yeast and detected hyperkinetic behaviors for chromatin-bound molecules that frequently transition to the free state for all complexes. Chromatin-bound remodelers display notably higher diffusion than nucleosomal histones, and strikingly fast dissociation kinetics with 4-7 s mean residence times. These enhanced dynamics require ATP binding or hydrolysis by the catalytic ATPase, uncovering an additional function to its established role in nucleosome remodeling. Kinetic simulations show that multiple remodelers can repeatedly occupy the same promoter region on a timescale of minutes, implicating an unending ‘tug-of-war’ that controls a temporally shifting window of accessibility for the transcription initiation machinery.

show abstract

Section: A Temporal Model For Nucleosome Remodeling At Ndrssupporting

confidence: 90%

Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Kim

Visanpattanasin

Jou

et al. 2021

eLife

View full text Add to dashboard Cite

show abstract

“…This suggests that although TFs can engage nucleosome-occupied DNA, they may require additional cofactors to persist at high levels on chromatin in vivo. Together with acute ablation or transient inhibition of remodeler activity, these studies have begun to reshape our understanding of site-specific gene activation within chromatin as a highly dynamic system (Iurlaro et al, 2021;Schick et al, 2021). Further time-resolved and molecular dissection of the interplay between site-specific TFs and ATP-dependent chromatin remodelers remains critical for our understanding of TF engagement and pioneer activity.…”

Section: Recognition Of Site-specific Dna Motifs In the Context Of A Nucleosomementioning

confidence: 99%

Reading the chromatinized genome

Michael

Thomä

2021

Cell

View full text Add to dashboard Cite

“…Our results reveal that FUS‐DDIT3 condensates can compartmentalize BRG1, a key catalytic subunit (ATPase) of mSWI/SNF that is responsible for ATP‐dependent remodeling of DNA‐histone interactions. Since a continuous activity of the mSWI/SNF is often required to maintain the appropriate chromatin state at the target genomic locus, 63,64 the selective enrichment of mSWI/SNF components by FUS‐DDIT3 condensates provides two possible routes to transcriptional reprograming (Figure 5). First, condensates of FET‐fusion proteins formed at ectopic genomic regions, as specified by binding sites of the DNA‐binding domain, can recruit BRG1 and modify local chromatin dynamics to activate transcription (Figure 5 left panel).…”

Section: Discussionmentioning

confidence: 99%

FUS oncofusion protein condensates recruit mSWI/SNF chromatin remodeler via heterotypic interactions between prion‐like domains

et al. 2021

View full text Add to dashboard Cite

Fusion transcription factors generated by genomic translocations are common drivers of several types of cancers including sarcomas and leukemias. Oncofusions of the FET (FUS, EWSR1, and TAF15) family proteins result from the fusion of the prion‐like domain (PLD) of FET proteins to the DNA‐binding domain (DBD) of certain transcription regulators and are implicated in aberrant transcriptional programs through interactions with chromatin remodelers. Here, we show that FUS‐DDIT3, a FET oncofusion protein, undergoes PLD‐mediated phase separation into liquid‐like condensates. Nuclear FUS‐DDIT3 condensates can recruit essential components of the global transcriptional machinery such as the chromatin remodeler SWI/SNF. The recruitment of mammalian SWI/SNF (mSWI/SNF) is driven by heterotypic PLD‐PLD interactions between FUS‐DDIT3 and core subunits of SWI/SNF, such as the catalytic component BRG1. Further experiments with single‐molecule correlative force‐fluorescence microscopy support a model wherein the fusion protein forms condensates on DNA surface and enrich BRG1 to activate transcription by ectopic chromatin remodeling. Similar PLD‐driven co‐condensation of mSWI/SNF with transcription factors can be employed by other oncogenic fusion proteins with a generic PLD‐DBD domain architecture for global transcriptional reprogramming.

show abstract

Acute BAF perturbation causes immediate changes in chromatin accessibility

Cited by 130 publications

References 64 publications

Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Single-molecule imaging of chromatin remodelers reveals role of ATPase in promoting fast kinetics of target search and dissociation from chromatin

Reading the chromatinized genome

FUS oncofusion protein condensates recruit mSWI/SNF chromatin remodeler via heterotypic interactions between prion‐like domains

Contact Info

Product

Resources

About