ATP-dependent chromatin remodeling: genetics, genomics and mechanisms
Open accessAbstract
Macromolecular assemblies that regulate chromatin structure using the energy of ATP hydrolysis have critical roles in development, cancer, and stem cell biology. The ATPases of this family are encoded by 27 human genes and are usually associated with several other proteins that are stable, non-exchangeable subunits. One fundamental mechanism used by these complexes is thought to be the movement or exchange of nucleosomes to regulate transcription. However, recent genetic studies indicate that chromatin remodelers may also be involved in regulating other aspects of chromatin structure during many cellular processes. The SWI/SNF family in particular appears to have undergone a substantial change in subunit composition and mechanism coincident with the evolutionary advent of multicellularity and the appearance of linking histones. The differential usage of this greater diversity of mammalian BAF subunits is essential for the development of specific cell fates, including the progression from pluripotency to multipotency to committed neurons. Recent human genetic screens have revealed that BRG1, ARID1A, BAF155, and hSNF5 are frequently mutated in tumors, indicating that BAF complexes also play a critical role in the initiation or progression of cancer. The mechanistic bases underlying the genetic requirements for BAF and other chromatin remodelers in development and cancer are relatively unexplored and will be a focus of this review.
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The Swi/Snf complex disrupts DNA-histone contacts and facilitates the local sliding or eviction of nucleosomes to modify DNA accessibility, and it often serves as a coactivator at highly induced promoters.
“The Swi/Snf complex disrupts DNA-histone contacts and facilitates the local sliding or eviction of nucleosomes to modify DNA accessibility, and it often serves as a coactivator at highly induced promoters (26–28).”
From Candida albicans Swi/Snf and Mediator Complexes Differentially Regulate Mrr1-Induced <i>MDR1</i> Expression and Fluconazole Resistance (2017) · cites this paper as [26]
The Mechanistic features section says SWI/SNF-mediated nucleosome sliding and perturbation promote DNA access, and the SWI/SNF family section says yeast SWI/SNF activates promoter targets alongside nucleosome displacement. The Early genetics section also describes its cooperation with transcriptional activators. Our copy does not establish that these promoters are highly induced or that the promoter-activating role applies equally to mammalian SWI/SNF-related complexes. (LLM, conf=0.85)
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“…chromatin (e.g., BRG1, BAF complex); (2) ISWI, which spaces nucleosomes for transcriptional regulation (e.g., SNF2H); (3) CHD, which contributes to nucleosome assembly and remodeling (e.g., CHD1, CHD8); and (4) INO80, which couples remodeling to DNA repair and replication (e.g., INO80, SRCAP) (40).”
- Authors
- Hargreaves, D. C., & Crabtree, G. R.
- Affiliations
- Howard Hughes Medical Institute (US)
- Corresponding author
- Crabtree, Gerald R
- Venue
- Cell Research
- Published
- 2011-03
- Volume
- 21
- Issue
- 3
- Pages
- 396-420
- ISSN
- 1001-0602 (ISSN-L)
- 1748-7838
- PMC
- PMC3110148
- OpenAlex
- W2080571195
- Cited by
- 923
- References
- 258
- Citations by year
- 2026: 30 · 2025: 40 · 2024: 47 · 2023: 54 · 2022: 69 · 2021: 67 · 2020: 56 · 2019: 46 · 2018: 47 · 2017: 58 · 2016: 59 · 2015: 63 · 2014: 80 · 2013: 95 · 2012: 80
- FWCI
- 8.09
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Cell Research (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Howard Hughes Medical Institute
- National Institute of Neurological Disorders and Stroke (R01NS046789)
- Eunice Kennedy Shriver National Institute of Child Health and Human Development (R01HD055391)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- chromatin remodeling, ATP-dependent chromatin remodeling, SWI/SNF complex, transcriptional regulation, evolution of multicellularity, histone modifications, cell fate specification, pluripotency, cancer, SMARCA4, ARID1A, BAF155, SMARCB1, chromatin remodeling genes
- MeSH terms
- Actins, Adenosine Triphosphatases, Adenosine Triphosphate, Chromosomal Proteins, Non-Histone, Humans, Saccharomyces cerevisiae, Transcription Factors, Chromatin Assembly and Disassembly
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