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FLASH GENE
Symbol PRDM16 contributors: mct/ - updated : 18-04-2017
HGNC name PR domain containing 16
HGNC id 14000
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • one N-positive regulatory (PR) domain, which is highly homologous to SET domain
  • ten C2H2-type zinc fingers
    • HOMOLOGY
    interspecies ortholog to murine Prmd16
    intraspecies homolog to MDS1/EVI1
    Homologene
    FAMILY
  • 16 PR domain-containing proteins family
    • CATEGORY transcription factor
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,cytoplasm,cytosolic
    intracellular,nucleus
    text
  • is localized in the nuclei of cardiomyocytes human development and in the adult heart
    • basic FUNCTION
  • involved in regulation of transcription, DNA-dependent
  • controls a bidirectional cell fate switch between skeletal myoblasts and brown fat cells
  • specifies the brown fat lineage from a progenitor that expresses myoblast markers and is not involved in white adipogenesis
  • transcription factor that regulates leukaemogenesis, palatogenesis and brown-fat development
  • functions in brown fat precursors to restrict skeletal muscle gene expression and development
  • controls a bidirectional cell fate switch between skeletal myoblasts and brown adipocytes
  • promotes stem cell maintenance in multiple tissues, partly by modulating oxidative stress
  • required for normal cell-cycle regulation and survival in haematopoietic stem cells and other primitive haematopoietic progenitors
  • in the central nervous system, appears to promote neural stem/progenitor cell function, partly by promoting HGF expression
  • implicated in the myocyte-adipocyte fate switch in skeletal muscle
  • may be a critical node in a network that contains negative and positive feedback loops and integrates hematopoietic stem cells renewal, quiescence, apoptosis and differentiation
  • MECOM and PRDM16 are H3K9me1 methyltransferases, and are essential for mammalian heterochromatin integrity
  • controls chromatin architecture and superenhancer activity in brown adipose tissue (BAT)
  • role of PRDM16 and its PR domain in the epigenetic regulation of myogenic and adipogenic genes during transdifferentiation of C2C12 myoblasts cells
  • MECOM and PRDM16 play additive roles in maintaining normal hematopoietic stem cell survival
    • CELLULAR PROCESS nucleotide, transcription, regulation
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA binding
    RNA
    small molecule metal binding,
  • Zn2+
    • protein
  • stimulates brown adipogenesis by binding to PPARG(peroxisome-proliferator-activated receptor-gamma) and activating its transcriptional function
  • interacted with SKI and inhibited TGF-beta signaling by stabilizing the inactive SMAD3-SKI complex on the promoter of TGF-beta target genes
  • concomitant MYOD1 and IGF2 inactivation accelerates differentiation of a brown preadipocyte cell line and induces lipid accumulation and increased UCP1 and PRDM16 expression
  • MECOM and PRDM16 initiate heterochromatin formation by inducing cytoplasmic H3K9me1, which is then converted in the nucleus by the SUV39H1 enzymes to H3K9me3
  • EHMT1 expression positively regulates the Brown adipose tissue (BAT)-selective thermogenic program by stabilizing the PRDM16 protein
  • PRDM16 is recruited to the UCP1 enhancer
  • enhances nuclear receptor-dependent transcription of the brown fat-specific UCP1 gene through interactions with Mediator subunit MED1
  • mechanistically, SRCAP recruits the transcriptional regulator REST to the PRDM16 promoter and induces expression of this transcription factor
    • cell & other
    REGULATION
    activated by activated in t(1;3)(p36;q21)-positive leukemia cells
    double MYOD1 and IGF2 inactivation (expression of PRDM16 involved in the switch between myogenic and brown adipogenic lineages was drastically enhanced by this inactivation)
    ASSOCIATED DISORDERS
    corresponding disease(s) LVNC8
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral fusion      
    fusion with RUNX1 in a patient with acute myeloid leukemia showing t(1;21)(p36;q22)
    tumoral     --over  
    in the t(1;3)(p36;q21)-positive MDS/AML cell lines
    tumoral     --other  
    aberrant gene expression associated with DNA hypomethylation is implicated in leukemogenesis of adult T-cell leukemia
    constitutional     --other  
    ectopic exression in myoblasts induces their differentiation into brown fat cells
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
    Therapy target
    SystemTypeDisorderPubmed
    obesity  
    inducing the expression of PRDM16 in white fat or muscle progenitors could be powerful in fighting obesity
    ANIMAL & CELL MODELS