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FLASH GENE
Symbol BRD2 contributors: mct - updated : 23-10-2019
HGNC name bromodomain containing 2
HGNC id 1103
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
  • BRD2, BRD3, BRD4, and BRDT are transcriptional regulators required for efficient expression of several growth promoting and antiapoptotic genes as well as for cell-cycle progression
  • 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
    SystemTypeDisorderPubmed
    cancer  
    inhibition of the BET-histone interaction results in transcriptional downregulation of a number of oncogenes, providing a novel pharmacologic strategy for the treatment of cancer
    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