What is the BAF complex?

What is the BAF complex?

Abstract. The ATP-dependent chromatin remodelling complex BAF (= mammalian SWI/SNF complex) is crucial for the regulation of gene expression and differentiation. In the course of evolution from yeast to mammals, the BAF complex evolved an immense complexity with a high number of subunits encoded by gene families.

How does SWI SNF work?

The SWI/SNF subfamily provides crucial nucleosome rearrangement, which is seen as ejection and/or sliding. The movement of nucleosomes provides easier access to the chromatin, allowing genes to be activated or repressed.

What does the SWI SNF complex do to DNA?

The SWI/SNF complex is a highly conserved protein complex across eukaryotes with a critical role in modulating transcription by promoting DNA accessibility. In mammals, the SWI/SNF complex (also known as Brg1-Associated Factors [BAF]), is encoded by 29 genes from 15 different gene families.

What is the SMARCA4 gene?

The SMARCA4 gene provides instructions for making a protein called BRG1, which forms one piece (subunit) of several different protein groupings called SWI/SNF protein complexes. SWI/SNF complexes regulate gene activity (expression) by a process known as chromatin remodeling.

What is the role of the SWI SNF complex?

The SWI/SNF complex functions as a master regulator of gene expression. SWI/SNF is a master regulator of gene expression. In mammalian cells, SWI/SNF has been linked to a large number of transcription factors.

Is SWI SNF a coactivator?

The core component of the mammalian SWI/SNF complex SMARCD3/BAF60c is a coactivator for the nuclear retinoic acid receptor. Mol Cell Endocrinol. 2007 May 30;270(1-2):23-32.

How does SWI SNF activate transcription?

Generally, the SWI/SNF complex mobilizes nucleosomes by utilizing the energy of ATP hydrolysis via the Swi/Snf2p subunit (mammalian orthologs are BRM or BRG1). As a result, the interface between histones and DNA is locally altered, and DNA is rendered accessible to basal transcription machinery [11], [12].

Is SMARCA4 hereditary?

Mutations in the SMARCA4 gene are inherited in an autosomal dominant fashion. This means that children, brothers, sisters, and parents of individuals with a SMARCA4 mutation have a 1 in 2 (50\%) chance of having the mutation as well.

What is SMARCA4 deficient thoracic sarcoma?

SMARCA4-deficient thoracic sarcoma (SMARCA4-DTS) is a recently described entity with a poor prognosis that is defined by certain genetic alterations in the BAF chromatin remodeling complex, specifically SMARCA4 and SMARCA2.

What is the role of the mediator complex in transcription?

Mediator is a multiprotein complex that functions as a transcriptional coactivator in all eukaryotes. Mediator complexes interact with transcription factors and RNA polymerase II. The main function of mediator complexes is to transmit signals from the transcription factors to the polymerase.

What is SMARCA4 mutation?

SMARCA4 is gene whose protein product participates in chromatin remodeling. Somatic mutations in this gene are associated with non-small cell lung cancer and malignant rhabdoid tumors, and both germline and somatic mutations are seen with small cell carcinoma of the ovary, hypercalcemic type.

Is the TATA box a protein?

This protein is active in cells and tissues throughout the body, where it plays an essential role in regulating the activity of most genes. The TATA box binding protein attaches (binds) to a particular sequence of DNA known as the TATA box.

What is the role of SWI/SNF complex in cancer?

Mammalian SWI/SNF complex is a key chromatin remodeler that reshapes nucleosomes and regulates DNA accessibility. Mutations in SWI/SNF subunits are found in a broad spectrum of human cancers; however, the mechanisms of how these aberrations of SWI/SNF complex would impact tumorigenesis and cancer therapeutics remain to be elucidated.

Is the mammalian BAF complex similar to the yeast SWI/SNF complex?

Reflecting this circumstance, the mammalian BAF complex is able to activate and repress genes, causing a limited comparability between the yeast SWI/SNF complex and those in more complex multicellular organisms [ 53, 54, 55 ]. Based on different subunit composition, two distinct BAF complexes have already been described.

What is the prevalence of swswi/SNF complex mutations?

SWI/SNF complex mutations are frequently observed in numerous human cancers, with an average mutation rate of 20\%, which ranks immediately after p53 (26\%) (Table 2) 2, 3, 4.

Can SWI/SNF deficiency be therapeutically targeted by ICB?

Emerging evidence has suggested that SWI/SNF components play novel roles in the regulation of anti-tumor immunity, and SWI/SNF deficiency can be therapeutically targeted by ICB. These findings manifest the prominence of the SWI/SNF complex as a stratification biomarker that predicts treatment (therapeutic) response to ICB.