Disease relevance of Brd2

• Transgenic mice with lymphoid-restricted overexpression of the double bromodomain protein bromodomain-containing 2 (Brd2) develop splenic B-cell lymphoma and, upon transplantation, B-cell leukemia with leukemic infiltrates in liver and lung [1].
• EXPERIMENTAL DESIGN: The cell lines used were SK-N-BE(2c) (human neuroblastoma) and UVW/NAT (glioma cell line transfected with the noradrenaline transporter gene) [2].

High impact information on Brd2

• Several DRIP/ARC subunits are also components of other potentially related cofactors, such as CRSP, NAT, SMCC and the mouse Mediator, indicating that unique classes of activators may share common sets or subsets of cofactors [3].
• Moreover association of Brd2, but not other bromodomain proteins, with acetylated chromatin persisted on chromosomes during mitosis [4].
• A previous report suggested that PARP-1-deficient mice also had a severe telomeric dysfunction consisting of telomere shortening and increased end-to-end fusions (d'Adda di Fagagna, F., M.P. Hande, W.-M. Tong, P.M. Lansdorp, Z.-Q. Wang, and S.P. Jackson. 1999. NAT: Genet. 23:76-80) [5].
• Peptide sequencing also identifies a component of mouse Mediator as a relative of Ring-3 protein, a mitogen-activated nuclear protein kinase, raising the possibility of Mediator as an end point of signal transduction pathways [6].
• The uniform increase of Ring3 expression in both Plasmodium- and Toxoplasma-infected livers suggests an innate immune response against parasitic infections, whereas the other gene expression changes are consistent with Plasmodium parasite-specific responses [7].

Biological context of Brd2

• The distinct patterns of Brd2 localization within the adult ovary supports a role for Brd2 in mitotic and possibly meiotic cell cycle regulation [8].
• Constructs were also generated in which the Fsrg1 cDNA was tagged with epitopes for hemaglutinin and used in transfection experiments [9].
• These results suggest that the Ring3 gene plays an important role in spermatogenesis [10].
• Furthermore, in situ hybridization on cross sections of seminiferous tubules in the testis showed that the expression of the Ring3 gene was initiated at the pachytene spermatocyte stage during meiosis and persisted throughout the round spermatid stage during spermiogenesis [10].
• Bromodomain analysis of Brd2-dependent transcriptional activation of cyclin A [11].

Anatomical context of Brd2

• Thus, Brd2 expression appears to correlate with stages of oocyte maturation, independent of FSH or GDF9 action and the subsequent disruption in normal follicle development in these models [8].
• Expression of mouse Brd2 has been shown previously to be expressed in specific patterns in proliferating cells in the developing alveoli in the mammary gland [12].
• These observations are consistent with our previous finding that nuclear localization of Brd2 protein correlates with an active cell cycle in mouse mammary alveoli during the reproductive cycle, and similar results from others in cultured fibroblasts [12].
• Brd2 mRNA was detected in brain vesicles, neural tube, spinal cord and dorsal root ganglia (DRG) [12].
• Northern blot hybridization analysis of adult tissues revealed that Fsrg1 was expressed at low levels rather ubiquitously, but most abundantly in the testis and ovary [9].

Associations of Brd2 with chemical compounds

• To determine the physiological relevance of these potential associations, we examined the patterns of expression of Fsrg1 mRNA and protein in the adult mammary epithelia during the reproductive cycle as the tissue is responding to estrogen, progesterone, and prolactin [13].
• Dimethylsulfoxide at concentrations used in the 2-aminofluorene acetylation assay in earlier studies, inhibited the A/J liver N-acetyltransferase to a greater extent than the C57BL/6J enzyme, which may have contributed to the larger difference in liver NAT activity with 2-aminofluorene reported previously [14].
• The spectrophotometric assay is characterized by two features: (i) NAT activity is measured by quantifying the disappearance of the arylamine substrate as reflected by decreasing Schiff's base formation with dimethylaminobenzaldehyde [15].
• Four TSNA-NNN, NNK, N'-nitrosoanatabine (NAT), and N'-nitrosoanabasine (NAB)-were analyzed by gas chromatography with nitrosamine selective detection (GC-TEA) [16].
• Four TSNA have thus far been identified; these are N'-nitrosonornicotine (NNN), 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone (NNK), N'-nitrosoanatabine (NAT) and N'-nitrosoanabasine (NAB) [17].

Regulatory relationships of Brd2

• Bromodomain containing 2 (Brd2) is expressed in distinct patterns during ovarian folliculogenesis independent of FSH or GDF9 action [8].

Other interactions of Brd2

• Expression and potential role of Fsrg1, a murine bromodomain-containing homologue of the Drosophila gene female sterile homeotic [9].

Analytical, diagnostic and therapeutic context of Brd2

• In the present study, in situ hybridization and immunohistochemical analyses were used to examine expression of Brd2 in developing neural tissues [12].
• Antibodies against murine Fsrg1 were generated and used in immunoblot and immunoprecipitation experiments to identify proteins interacting with Fsrg1 and RING3 [13].

References