Evidence map›Paper›PMID 33053319›Full record

ArticleCell2020

A Structural Model of the Endogenous Human BAF Complex Informs Disease Mechanisms.

Nazar Mashtalir, Hiroshi Suzuki, Daniel P Farrell, Akshay Sankar, Jie Luo, Martin Filipovski, Andrew R D'Avino, Roodolph St Pierre, Alfredo M Valencia, Takashi Onikubo and 7 more

Open access · bronzeAbstract read
In one paragraph

Article in Cell, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 130 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
130citing papers in PubMed, 1 pooled it
8.2field-weighted citation impact, top 2% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

130 citing papers in PubMed, 1 synthesis or guideline pooled it, 196 citations in OpenAlex.

  1. Guideline
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  6. Structure and molecular function of the BCL7 proteins.Biochemical Society transactions · 2026
    Review
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70 more citing papers are in PubMed but not listed here.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

17 authors at 5 institutions in 1 country.

Nazar MashtalirDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Hiroshi SuzukiLaboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY, USA.
Daniel P FarrellDepartment of Biochemistry, University of Washington, Seattle, WA, USA.
Akshay SankarDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Jie LuoInstitute for Systems Biology, Seattle, WA, USA.
Martin FilipovskiDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Andrew R D'AvinoDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA.
Roodolph St PierreDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Chemical Biology Program, Harvard Medical School, Boston, MA, USA.
Alfredo M ValenciaDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA; Chemical Biology Program, Harvard Medical School, Boston, MA, USA.
Takashi OnikuboLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY, USA.
Robert G RoederLaboratory of Biochemistry and Molecular Biology, The Rockefeller University, New York, NY, USA.
Yan HanDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Yuan HeDepartment of Molecular Biosciences, Northwestern University, Evanston, IL, USA.
Jeffrey A RanishInstitute for Systems Biology, Seattle, WA, USA.
Frank DiMaioDepartment of Biochemistry, University of Washington, Seattle, WA, USA. Electronic address: dimaio@u.washington.edu.
Thomas WalzLaboratory of Molecular Electron Microscopy, The Rockefeller University, New York, NY, USA. Electronic address: twalz@rockefeller.edu.
Cigall KadochDepartment of Pediatric Oncology, Dana-Farber Cancer Institute and Harvard Medical School, Boston, MA, USA; Broad Institute of MIT and Harvard, Cambridge, MA, USA. Electronic address: cigall_kadoch@dfci.harvard.edu.
Broad Institute · USRockefeller University · USInstitute for Systems Biology · USNorthwestern University · USUniversity of Washington · US

Funding

Transcription-Coupled & Replication-Associated Excision RepairP01CA092584 · NCI · UNIVERSITY OF CALIF-LAWRENC BERKELEY LAB · PI John A. Tainer · 2001 to 2026
$89.6M
Spatio-Temporal Organization of Chromatin and Information Transfer in CancerU54CA193419 · NCI · NORTHWESTERN UNIVERSITY AT CHICAGO · PI MARKO, JOHN F · 2015 to 2020
$10.4M
Molecular mechanisms of estrogen receptor-dependent transcription regulationR01CA234575 · NCI · ROCKEFELLER UNIVERSITY · PI ROEDER, ROBERT G · 2019 to 2023
$3.1M
Reversing Oncogenic BAF Complex Structure & Function: New Therapeutic ApproachesDP2CA195762 · NCI · DANA-FARBER CANCER INST · PI KADOCH, CIGALL · 2014 to 2014
$2.6M
TFIIH and Transcription RegulationR01GM110064 · NIGMS · UNIVERSITY OF COLORADO · PI RANISH, JEFFREY A, TAATJES, DYLAN J · 2016 to 2019
$2.2M
Structure and Mechanism of Non-Homologous End JoiningR01GM135651 · NIGMS · NORTHWESTERN UNIVERSITY · PI HE, YUAN · 2020 to 2024
$1.8M
Structure and Function of ATP-Dependent Chromatin Remodeling Complexes in Human CancerK99CA237855 · NCI · DANA-FARBER CANCER INST · PI MASHTALIR, NAZAR · 2019 to 2020
$278k
NCI NIH HHS DP2 CA195762NCI NIH HHS K99 CA237855NCI NIH HHS P01 CA092584NCI NIH HHS R01 CA234575NIGMS NIH HHS R01 GM110064NIGMS NIH HHS R01 GM135651
6 · The paper itself

Abstract

Mammalian SWI/SNF complexes are ATP-dependent chromatin remodeling complexes that regulate genomic architecture. Here, we present a structural model of the endogenously purified human canonical BAF complex bound to the nucleosome, generated using cryoelectron microscopy (cryo-EM), cross-linking mass spectrometry, and homology modeling. BAF complexes bilaterally engage the nucleosome H2A/H2B acidic patch regions through the SMARCB1 C-terminal α-helix and the SMARCA4/2 C-terminal SnAc/post-SnAc regions, with disease-associated mutations in either causing attenuated chromatin remodeling activities. Further, we define changes in BAF complex architecture upon nucleosome engagement and compare the structural model of endogenous BAF to those of related SWI/SNF-family complexes. Finally, we assign and experimentally interrogate cancer-associated hot-spot mutations localizing within the endogenous human BAF complex, identifying those that disrupt BAF subunit-subunit and subunit-nucleosome interfaces in the nucleosome-bound conformation. Taken together, this integrative structural approach provides important biophysical foundations for understanding the mechanisms of BAF complex function in normal and disease states.

Indexed as

DiseaseModels, MolecularChromatin Assembly and DisassemblyCryoelectron MicroscopyDNA HelicasesHumansMultiprotein ComplexesMutation, MissenseNuclear ProteinsNucleosomesProtein BindingProtein DomainsProtein SubunitsSaccharomyces cerevisiaeStructural Homology, ProteinTranscription FactorsDNA HelicasesMultiprotein ComplexesNuclear ProteinsNucleosomesProtein SubunitsSMARCA4 protein, humanTranscription FactorsATP-dependent chromatin remodelingBAF complexcancercross-linking mass spectrometrycryoelectron microscopyhomology modelingmammalian SWI/SNF complexesmutations

Identifiers

PMID33053319
PMCPMC7717177
OpenAlexW3092921638

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.