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FLASH GENE
Symbol BRD2 contributors: mct - updated : 23-10-2019
HGNC name bromodomain containing 2
HGNC id 1103
Corresponding disease
EJM3 myoclonic epilepsy, juvenile, 3
Location 6p21.32      Physical location : 4.168.580 - 32.949.281
Synonym name
  • female sterile homeotic-related gene 1
  • really interesting new gene 3
  • Synonym symbol(s) NAT, RNF3, FSRG1, RING3, D6S113E, KIAA9001, DKFZp686N0336, FLJ31942,
    DNA
    TYPE functioning gene
    STRUCTURE 12.85 kb     13 Exon(s)
    10 Kb 5' upstream gene genomic sequence study
    regulatory sequence Promoter
    cytosine-phosphate-guanine/HTF
    text structure
  • a CpG island
  • DNA demethylation of the BRD2 promoter region induced BRD2 expression during differentiation of 3T3-L1 cells into adipocytes
  • MAPPING cloned Y linked N status provisional
    regionally located . located to the major histocompatibility complex (MHC) class II region, between HLA-DMA
    RNA
    TRANSCRIPTS type messenger
    identificationnb exonstypebpproduct
    ProteinkDaAAspecific expressionYearPubmed
    13 - 4907 - 801 - 1997 9373153
    13 - 4807 - 801 - 1997 9373153
    13 - 4602 - 836 - 1997 9373153
    12 - 3210 - 754 - 1997 9373153
    14 - 4853 - 681 - 1997 9373153
    EXPRESSION
    Type ubiquitous
       expressed in (based on citations)
    organ(s)
    SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
    Endocrinepancreas   highly Homo sapiens
     thyroid   highly
    Lymphoid/Immunespleen   highly
     thymus   highly
    Nervousbrainlimbic systemhippocampus highly Homo sapiens BRD2 mRNA
     brainhindbraincerebellum   Homo sapiensBRD2 mRNA
    Reproductivemale systemtestis   
    tissue
    SystemTissueTissue level 1Tissue level 2LevelPubmedSpeciesStageRna symbol
    Epithelialbarrier/lining   
    cells
    SystemCellPubmedSpeciesStageRna symbol
    Cardiovascularendothelial cell
    Endocrineislet cell (alpha,beta...) Homo sapiens
    Skin/Tegumentkeratinocyte
    cell lineage
    cell lines
    fluid/secretion
    at STAGE
    physiological period embryo
    Text highest expression of Brd2 is detected in the developing neural tube
    PROTEIN
    PHYSICAL PROPERTIES
    STRUCTURE
    motifs/domains
  • common domain architecture featuring two N-terminal bromodomains that exhibit high levels of sequence conservation (inhibitor JQ1 binds to the Kac binding site of BET bromodomains), a dual bromodomains
  • an extraterminal domain
  • BRD2-BD1 recognizes the H4 tail acetylated at Lys-12 (H4K12ac)
  • a PEST domain
  • one ET domain
  • a RING finger motif
  • a more divergent C-terminal recruitment domain, that is important for chromatin interaction and regulation of transcription and alternative splicing
  • HOMOLOGY
    interspecies homolog to murine Rnf3
    homolog to Drosophila Fsh
    intraspecies paralog to BRD3 (52 p100)
    Homologene
    FAMILY bromodomain and extra-terminal (BET) family
    CATEGORY enzyme
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm
    intracellular,nucleus,nucleoplasm,nuclear bodies,nuclear speckles
    intracellular,nucleus,chromatin/chromosome
    text mainly localizes in nucleus in two distribution patterns, diffused and dotted
    basic FUNCTION
  • protein serine/threonine kinase, identified by the monoclonal antibody LY9, overexpressed in proliferating endothelial cells
  • mitogen-activated kinase
  • translocating in the nucleus the promoter of a number of the E2 family of transcription factors
  • playing a role in regulating brain development
  • having distinct roles in initiating apoptosis, and the dotted distribution pattern in nucleus may be a morphologic marker of cell apoptosis
  • TBP-associated protein recruiting TBP into E2F1 transcriptional complex in response to serum stimulation
  • has intrinsic histone chaperone activity and is required for transcription of the cyclin D1 gene
  • required for the completion of embryogenesis and proper neural tube closure during development
  • transcriptional co-activator/co-repressor with SWI/SNF (switch mating type/sucrose non-fermenting)-like functions that regulates chromatin
  • BET family members have been recognized as essential genes for the replication of viruses and in mediating inflammatory responses
  • BET family proteins recognize acetylated chromatin through their two bromodomains, acting as transcriptional activators or tethering viral genomes to the mitotic chromosomes of their host
  • BRD2 is likely required for cell cycle exit and neuronal differentiation of neuroepithelial cells through the E2F1 pathway during CNS development
  • transcriptional coregulator, that couples chromatin to cell-cycle progression
  • plays a critical, independent role in regulation of mitogenic response genes, particularly cyclin A, in B cells
  • suppresses adipocyte differentiation
  • antagonistic relationship between H2AZ1 monoubiquitylated and BRD2 to regulate the transcriptional balance at bivalent genes to enable proper execution of developmental programs
  • separate and interdependent BRD2 and BRD4 functions in potentiating the genetic program required for Th17 cell development and adaptive immunity
  • BRD2 therefore creates a restricted chromatin environment surrounding DSBs which facilitates DSB repair and which is framed by extensive ZMYND8 domains on the flanking chromatin
  • CELLULAR PROCESS cell life, cell death/apoptosis
    nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS development , reproduction/sex
    text spermatogenesis
    PATHWAY
    metabolism
    signaling signal transduction
    signal transduction pathway involved in growth control
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
    Zn2+
    protein
  • interacting with BRD7
  • is specifically localized at promoters of target genes, and BRD2 interaction with chromatin cannot be explained solely by histone acetylation
  • PTN antagonized the cell-cycle-stimulating activity associated with BRD2, thus enhancing induced neuronal differentiation
  • DNA methylation contributes to the regulation of BRD2 expression during pre-adipocyte differentiation (pMID: 25575605)
  • is associated with the chromatin insulator CTCF and the cohesin complex to support cis-regulatory enhancer assembly for gene transcriptional activation
  • CTCF recruits BRD2 to co-bound sites whereas BRD2 is dispensable for CTCF occupancy and BRD2 cooperates with CTCF to enforce transcriptional and architectural boundaries
  • BRD2 facilitates recruitment of a second bromodomain protein, ZMYND8, which spreads along the flanking chromatin, but is excluded from the DNA double-strand breaks region
  • cell & other
  • interacts with acetylated chromatin during mitosis and leads to transcriptional activation in culture cells
  • REGULATION
    inhibited by JQ1, a selective and potent inhibitor of BET family bromodomains
    Other increased by VPF/VGEF165
    regulated at transcription, splicing, and translation levels
    ASSOCIATED DISORDERS
    corresponding disease(s) EJM3
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in certain types of leukemia
    Susceptibility to juvenile myoclonic epilepsy
    Variant & Polymorphism SNP , other polymorphisms confering increased risk of juvenile myoclonic epilepsy
    Candidate gene
    Marker
    Therapy target
    ANIMAL & CELL MODELS
  • disruption of Brd2, an unusual MHC gene, causes lifelong severe obesity in mice with pancreatic islet expansion, hyperinsulinaemia, hepatosteatosis and elevated pro-inflammatory cytokines, but, surprisingly, enhanced glucose tolerance, elevated adiponectin, increased weight of brown adipose tissue
  • viable Brd2(+/-) heterozygotes mice show both decreased GABAergic neuron counts and increased susceptibility to seizures