Disease relevance of Smarca2

• We show that Brm and MeCP2 assembly on chromatin occurs on methylated genes in cancer and the gene FMR1 in fragile X syndrome [1].
• Both Brg1 and Brm are mutated or deleted in numerous cancer cell lines, leading to the altered expression of genes that influence cell proliferation and metastasis [2].

High impact information on Smarca2

• Brahma links the SWI/SNF chromatin-remodeling complex with MeCP2-dependent transcriptional silencing [1].
• These results provide molecular explanations for the transcriptional repression state of cyclin A, as well as insights into the action of Brm chromatin remodeling factor as cell cycle regulator [3].
• Mammalian SWI/SNF complexes utilize either brahma (Brm) or brahma-related gene 1 (Brg1) catalytic subunits to remodel nucleosomes in an ATP-dependent manner [4].
• Altered control of cellular proliferation in the absence of mammalian brahma (SNF2alpha) [5].
• We show here that the expression of brm, but not BRG-1, is negatively regulated by mitogenic stimulation, and that growth arrest of mouse fibroblasts leads to increased accumulation of the brm protein [6].

Biological context of Smarca2

• Within this complex, the BRM (SNF2alpha) and BRG1 (SNF2beta) proteins are mutually exclusive subunits that are believed to affect nucleosomal structures using the energy of ATP hydrolysis [5].
• In the present study, we have examined the ability of various brm/SNF2alpha deletion mutants to reverse the transformed phenotype of ras-transformed fibroblasts [7].
• The region has homology to the AT hooks present in high-mobility-group protein I/Y DNA binding domains and is required for the tethering of brm/SNF2alpha to chromatin [7].
• This region was also required for cooperation of brm/SNF2alpha with the glucocorticoid receptor in transfection experiments, but only in the context of a reporter construct integrated in the cellular genome [7].
• In vivo, Brm-deficient mice also show methylation and silencing of the CD44 promoter [2].

Anatomical context of Smarca2

• We show that BRG1 is selectively required for epithelial-mesenchymal interactions in limb patterning, and during keratinocyte terminal differentiation, in which BRM can partially substitute for BRG1 [8].
• The decline in hepatic progenitor cell proliferation owing to the formation of a complex involving cEBP-alpha and the chromatin remodelling factor brahma (Brm) inhibits the regenerative capacity of aged liver [9].

Associations of Smarca2 with chemical compounds

• In this study, we analyse expression of tPA, Grik2, Smarca2 and the transcription factor, Sp1, in mouse cerebellum following acute ethanol treatment [10].
• Effect of Brahma Rasayana on antioxidant systems and cytokine levels in mice during cyclophosphamide administration [11].

Other interactions of Smarca2

• The activity of mammalian brm/SNF2alpha is dependent on a high-mobility-group protein I/Y-like DNA binding domain [7].
• Animal SWI2/SNF2 protein complexes containing either the brahma (BRM) or brahma-related gene 1 (BRG1) ATPase are involved in nucleosome remodelling and may control the accessibility of sequence-specific transcription factors to DNA [8].
• Antioxidant activity of brahma rasayana [12].

Analytical, diagnostic and therapeutic context of Smarca2

• We used a number of different molecular approaches and chromatin immunoprecipitation strategies to show a unique cooperation between Brm, BAF57 and MeCP2 [1].

References