Disease relevance of brm

• Thus, homozygous BRM loss of function mutants are viable but exhibit numerous defects including dwarfism, altered leaf and root development and several reproduction defects [1].

High impact information on brm

• The brahma (brm) gene is required for the activation of multiple homeotic genes in Drosophila [2].
• The Drosophila brahma complex is an essential coactivator for the trithorax group protein zeste [3].
• Reconstituted transcription reactions established that the Brahma (BRM) chromatin-remodeling complex is essential for Zeste-directed activation on nucleosomal templates [3].
• Osa-containing Brahma chromatin remodeling complexes are required for the repression of wingless target genes [4].
• Receptor binding to minichromosomes recruits ISWI and NURF38, but not brahma [5].

Biological context of brm

• We first screened for dominant mutations that are lethal in combination with a brm(K804R) transgene under control of the brm promoter [6].
• Allele-specific genetic interactions between snr1(E1) and mutations in genes encoding other members of the Brm complex suggest that snr1(E1) mutant phenotypes result from reduced Brm complex function [7].
• Genetic screens for enhancers of brahma reveal functional interactions between the BRM chromatin-remodeling complex and the delta-notch signal transduction pathway in Drosophila [6].
• A widespread distribution of SNR1 and BRM on the salivary gland polytene chromosomes showed that the Brm complex associated with many genes, but not always at transcribed loci, consistent with genetic data suggesting roles in both gene activation and repression [8].
• Among the trithorax group proteins characterized, the BRAHMA protein appears to be a subunit of a protein complex conserved from yeast to man (the SNF/SWI complex) that modifies chromatin to facilitate the transcriptional activation by gene-specific DNA-binding proteins [9].

Anatomical context of brm

• Using mosaic analysis, we found that the complete loss of brm function decreases cell viability and causes defects in the peripheral nervous system of the adult [10].

Associations of brm with chemical compounds

• A dominant-negative brm mutation was generated by replacing a conserved lysine in the ATP-binding site of the BRM protein with an arginine [10].
• SYT has a conserved N-terminal domain (SNH domain) that interacts with the human paralog of Drosophila Brahma (hBRM) and Brahma-related gene 1 (BRG1) chromatin remodeling proteins and a C-terminal transactivating sequence rich in glutamine, proline, glycine, and tyrosine (QPGY domain) [11].

Physical interactions of brm

• The trithorax group gene osa encodes an ARID-domain protein that genetically interacts with the brahma chromatin-remodeling factor to regulate transcription [12].
• Drosophila cyclin E interacts with components of the Brahma complex [13].
• We propose that the OSA protein may target the BRM complex to Antennapedia and other regulated genes [12].
• Our results reveal that SNR1 helps mediate associations between the Brm complex and DmcycE/CDK2 both in vitro and in vivo [14].
• High mobility group proteins HMGD and HMGZ interact genetically with the Brahma chromatin remodeling complex in Drosophila [15].

Regulatory relationships of brm

• Despite essential Brm complex functions in leg development, genetic and protein localization studies revealed that snr1 was not required or expressed in all tissues dependent on Brm complex activities [8].
• Furthermore, heterozygosity for BAP111 enhanced the phenotypes resulting from a partial loss of brm function [16].

Other interactions of brm

• The trithorax group gene moira encodes a brahma-associated putative chromatin-remodeling factor in Drosophila melanogaster [17].
• To identify direct regulatory targets of the Brm complex, we performed oligonucleotide-based transcriptome microarray analyses using RNA isolated from mutant fly strains harboring dominant-negative alleles of snr1 and brm [18].
• Because it is not required for Zeste to bind to chromatin, the BRM complex appears to act after promoter binding by the activator [3].
• These findings suggest that BRM plays a role in chromatin remodeling that is distinct from the function of most other trithorax group proteins [19].
• Hormone-response Genes Are Direct in Vivo Regulatory Targets of Brahma (SWI/SNF) Complex Function [18].

Analytical, diagnostic and therapeutic context of brm

• By using gel filtration chromatography and immunoprecipitation assays, we found that the majority of BAP111 protein in embryos is associated with the BRM complex [16].
• Site-directed mutagenesis was used to investigate the functions of conserved regions of the BRM protein [10].

References