The SWI/SNF ATP-dependent chromatin remodeling complex in cell lineage priming and early development.

Biochem Soc Trans

Department of Epigenetics and Molecular Carcinogenesis, Center for Cancer Epigenetics, University of Texas MD Anderson Cancer Center, Houston, TX 77054, U.S.A.

Published: April 2024

ATP dependent chromatin remodelers have pivotal roles in transcription, DNA replication and repair, and maintaining genome integrity. SWI/SNF remodelers were first discovered in yeast genetic screens for factors involved in mating type switching or for using alternative energy sources therefore termed SWI/SNF complex (short for SWItch/Sucrose NonFermentable). The SWI/SNF complexes utilize energy from ATP hydrolysis to disrupt histone-DNA interactions and shift, eject, or reposition nucleosomes making the underlying DNA more accessible to specific transcription factors and other regulatory proteins. In development, SWI/SNF orchestrates the precise activation and repression of genes at different stages, safe guards the formation of specific cell lineages and tissues. Dysregulation of SWI/SNF have been implicated in diseases such as cancer, where they can drive uncontrolled cell proliferation and tumor metastasis. Additionally, SWI/SNF defects are associated with neurodevelopmental disorders, leading to disruption of neural development and function. This review offers insights into recent developments regarding the roles of the SWI/SNF complex in pluripotency and cell lineage primining and the approaches that have helped delineate its importance. Understanding these molecular mechanisms is crucial for unraveling the intricate processes governing embryonic stem cell biology and developmental transitions and may potentially apply to human diseases linked to mutations in the SWI/SNF complex.

Download full-text PDF

Source
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC11088921PMC
http://dx.doi.org/10.1042/BST20230416DOI Listing

Publication Analysis

Top Keywords

swi/snf complex
12
swi/snf
9
cell lineage
8
cell
5
swi/snf atp-dependent
4
atp-dependent chromatin
4
chromatin remodeling
4
complex
4
remodeling complex
4
complex cell
4

Similar Publications

The ARID1A gene, frequently mutated in cancer, encodes the AT-rich interactive domain-containing protein 1 A, a key component of the chromatin remodeling SWI/SNF complex. The ARID1A protein features a conserved DNA-binding domain (ARID domain) of approximately 100 residues crucial for its function. Despite the frequency of mutations, the impact on ARID1A's stability and contribution to cancer progression remains unclear.

View Article and Find Full Text PDF

Rhabdoid tumours (RT) are an aggressive malignancy affecting <2-year-old infants, characterised by biallelic loss-of-function alterations in SWI/SNF-related BAF chromatin remodelling complex subunit B1 (SMARCB1) in nearly all cases. Germline SMARCB1 alterations are found in ~30% of patients and define the RT Predisposition Syndrome type 1 (RTPS1). Uveal melanoma (UVM), the most common primary intraocular cancer in adults, does not harbour SMARCB1 alterations.

View Article and Find Full Text PDF

The tumor suppressor gene SMARCA4, a critical component of the SWI/SNF chromatin remodeling complex, is frequently inactivated in various cancers, including clear cell renal cell carcinoma (ccRCC). Despite its significance, the role of SMARCA4 in ccRCC development and its potential therapeutic vulnerabilities have not been fully explored. Our research found that SMARCA4 deficiency was associated with poor prognosis and was observed in a subset of high-grade ccRCCs.

View Article and Find Full Text PDF

The cell death receptor FAS and its ligand (FASLG) play crucial roles in the selection of B cells during the germinal center (GC) reaction. Failure to eliminate potentially harmful B cells via FAS can lead to lymphoproliferation and the development of B cell malignancies. The classic form of follicular lymphoma (FL) is a prototypic GC-derived B cell malignancy, characterized by the t(14;18)(q32;q21)IGH::BCL2 translocation and overexpression of antiapoptotic BCL2.

View Article and Find Full Text PDF

Epigenetic Regulation Via Electrical Forces.

Rev Physiol Biochem Pharmacol

January 2025

Institute of Medical Sciences, University of Aberdeen, Aberdeen, Scotland, UK.

Multiple epigenetic modulations occur to chromatin rather than to DNA itself and these influence gene expression or gene silencing profoundly. Both the creation of these post-translational modifications and the mechanisms of their readout are regulated significantly by electrical forces several of which are discussed. They are also influenced by phase separation which itself is driven by electrical forces.

View Article and Find Full Text PDF

Want AI Summaries of new PubMed Abstracts delivered to your In-box?

Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!