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Chunk #4 — The Role of BRG1 in Cancer Epigenetics is Context Dependent

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Mammalian SWI/SNF Enzymes and the Epigenetics of Tumor Cell Metabolic Reprogramming.
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Chromatin structure presents a barrier to transcription factors and polymerases accessing DNA. Several multiprotein complexes alter chromatin structure using the energy derived from ATP-hydrolysis (32–34), including the mammalian SWI/SNF family of chromatin modifiers, which are large, multisubunit enzymes that contain one of two closely related ATPases called BRM or BRG1 (35–37). SWI/SNF complexes containing either catalytic subunit alter nucleosome structure and facilitate binding of transcription factors to nucleosomal DNA in an ATP-dependent manner (38, 39). Subunits of the mammalian SWI/SNF complexes are important for gene activation and repression, development and differentiation, recombination and repair, cell cycle control, and tumorigenesis (40–43). For example, the SNF5 (INI1) subunit is required for embryonic development and functions as a tumor suppressor (44–46).