Disease relevance of BRD2

• Kaposi's Sarcoma-Associated Herpesvirus LANA-1 Interacts with the Short Variant of BRD4 and Releases Cells from a BRD4- and BRD2/RING3-Induced G1 Cell Cycle Arrest [1].
• E mu-BRD2 transgenic mice develop B-cell lymphoma and leukemia [2].
• Current US minipool HIV NAT screening protocols may not be sufficiently sensitive to detect all infectious window-period donations [3].
• MAIN OUTCOME MEASURES: Genetic analysis of the HIV-1 p17 coding region of gag and the C2V5 region of env to determine the genetic relatedness of virus from the donor and recipients; reactivity in quantitative and qualitative assays, and reactivity in donor screening HIV NAT assays in single donation and minipool screening contexts [3].
• The prediction of neonatal alloimmune thrombocytopenia (NATP) in affected families has, in the past, been based on information about gene frequencies of the antigen systems involved, parental phenotyping, and fetal platelet counts [4].

Psychiatry related information on BRD2

• Correlations between NAT variables and neuropsychological tests suggest the executive control deficits associated with VaD may contribute to specific action difficulties, such as distractor interference and inefficient, error-prone action on complex tasks [5].
• While the groups did not differ in dementia severity or overall impairment on the NAT, the VaD group committed more errors (3.3 vs. 1.6, p = 02) [5].
• This study examines differences between individuals diagnosed with vascular dementia (VaD; n = 25) versus Alzheimer's disease (AD; n = 23) on the Naturalistic Action Test (NAT; Schwartz et al., 2003), a performance-based measure that includes three tasks of increasing complexity [5].
• The purpose of this study was to determine whether polymorphisms in the human NAT genes influence susceptibility to Alzheimer's disease [6].

High impact information on BRD2

• The ARC complex consists of 16 or more subunits; some of these are novel gene products, whereas others are present in other multisubunit cofactors, such as CRSP, NAT and mammalian Mediator [7].
• OBJECTIVES: To determine HIV-1 genetic linkage between virus in 2 HIV-1-infected recipients of blood components and virus in the donor, who was HIV antigen and antibody negative at the time of donation; to screen the blood donor's plasma with HIV NAT assays, including those currently proposed for use in US blood donation screening [3].
• DNA sequencing revealed two JME-associated SNP variants in the BRD2 (RING3) promoter region but no other potentially causative coding mutations in 20 probands from families with positive LOD scores [8].
• In the present study, we found highly significant linkage disequilibrium (LD) between JME and a core haplotype of five single-nucleotide-polymorphism (SNP) and microsatellite markers in this critical region, with LD peaking in the BRD2 (RING3) gene (odds ratio 6.45; 95% confidence interval 2.36-17.58) [8].
• BRD2 (RING3) is a probable major susceptibility gene for common juvenile myoclonic epilepsy [8].

Chemical compound and disease context of BRD2

• NAT was identified recently in Mycobacterium tuberculosis and is a candidate for modulating the response to isoniazid [9].
• A new platelet alloantigen, termed CA, has recently been implicated in a case of neonatal alloimmune thrombocytopenia (NATP) in a Filipino family in Canada. Maternal anti-CA serum reacted with glycoprotein (GP) IIIa and maintained its reactivity after removal of high mannose carbohydrate residues from GPIIIa [10].
• In this report, we demonstrate an interaction between subtilisin NAT (formerly designated BSP, or nattokinase), a profibrinolytic serine proteinase from Bacillus subtilis, and plasminogen activator inhibitor 1 (PAI-1) [11].
• Conjugation of primary amino and hydroxylamino groups with acetate, catalyzed by acetyl CoA-dependent arylamine acetyltransferase (NAT) enzymes, may play an important role in the intricate series of metabolic pathways that produce or prevent toxicity following exposure to homo- and heterocyclic arylamine and hydrazine xenobiotics [12].
• The NAT activities of Klebsiella pneumoniae were inhibited by ibuprofen in a dose-dependent manner both in vitro and in vivo [13].

Biological context of BRD2

• Crystal Structure of the Human BRD2 Bromodomain: INSIGHTS INTO DIMERIZATION AND RECOGNITION OF ACETYLATED HISTONE H4 [14].
• Furthermore, ectopic expression of Rb protein, a negative regulator of E2F activity, suppresses the RING3-dependent transactivation of this promoter [15].
• Its nucleotide sequences suggested that it represented a new non-HLA gene with a single copy which was of little genetic polymorphism and named NAT (DNA-associated transcript) [16].
• Phylogeny and structure of the RING3 gene [17].
• The RING3 gene maps in the class II region of the human major histocompatibility complex, at a CpG island distal of the HLA-DNA gene [18].

Anatomical context of BRD2

• RING3 transforms NIH/3T3 cells and is activated by mitogenic signals, all of which suggest that it may play a role in cell cycle-responsive transcription [15].
• Identification and cloning of an 85-kDa protein homologous to RING3 that is upregulated in proliferating endothelial cells [19].
• RING3 cDNAs were obtained from a T cell cDNA library and the longest (4 kb) was sequenced [18].
• Constitutive expression of BRD2 in the lymphoid compartment increases cyclin A transcription, "priming" transgenic B cells for proliferation [2].
• We use immunostaining and confocal microscopy to demonstrate that RING3 translocates to the fibroblast nucleus upon serum stimulation [20].

Associations of BRD2 with chemical compounds

• High-molecular-mass complexes (1 to 2 MDa) sharing several subunits but apparently differing in others include the TRAP/SMCC, NAT, DRIP, ARC, and human Mediator complexes [21].
• These data strongly suggest that defective arylamine N-acetylation in the rabbit model is caused by a gene deletion resulting in an absence of specific mRNA and NAT enzyme protein [22].
• The first three-dimensional structure of a member of the NAT family identifies a catalytic triad consisting of aspartate, histidine and cysteine proposed to form the activation mechanism [9].
• Arylamine N:-acetyltransferase (NAT) was first identified as the inactivator of the anti-tubercular drug isoniazid [9].
• We explored the feasibility of allele-specific oligonucleotide probe typing for PIA antigens to determine the risk of second or subsequent fetuses in families where one infant had a diagnosis of anti-PIA1-mediated NATP [4].

Other interactions of BRD2

• RING3 and ORFX are found to be ubiquitously expressed in human adult and foetal tissues [23].
• DNA sequencing of this clone and predicted amino acids showed more than 93% homology to RING3 kinase, a member of a newly described family of bromodomain-containing proteins that transactivates in the nucleus the promoters of a number of the E2F family of transcription factors [19].
• The class II region of the human MHC contains all of the known class II genes: as well as antigen processing components and only one gene not obviously associated with the immune system, RING3 [24].
• Association of BRD2 polymorphisms with photoparoxysmal response [25].
• We present a dense STR/linkage disequilibrium(LD)/gene map between the RING3 and HLA-B loci, reference allelic sizes on the most prevalent HLA haplotypes and their allelic frequencies in pedigree founders [26].

Analytical, diagnostic and therapeutic context of BRD2

• Northern blot analysis showed that the NAT gene was expressed with a 4-kb transcript in all of tissues examined so far [16].
• Tissue was fixed for immunohistochemistry with specific NAT antibodies [27].
• Here, we report that synthetic gallosilicate molecular sieves with the NAT topology and Si/Ga ratios close to but slightly higher than 1.50 undergo an in situ transformation under their crystallization conditions [28].
• The potential effect of the NAT genotypes in individual susceptibility to lung cancer was examined in a hospital based case-control study consisting of 392 Caucasian lung cancer patients [152 adenocarcinomas, 173 squamous cell carcinomas (SCC) and 67 other primary lung tumours] and 351 controls [29].
• CONCLUSIONS: This case suggests that, at least in some newly infected individuals, the HCV viral load can fluctuate dramatically prior to seroconversion, and that NAT, even on individual samples, will not totally prevent HCV transmission [30].

References