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FLASH GENE
Symbol KDM6B contributors: mct/npt/pgu - updated : 08-02-2022
HGNC name lysine (K)-specific demethylase 6B
HGNC id 29012
EXPRESSION
Type widely
   expressed in (based on citations)
organ(s)
SystemOrgan level 1Organ level 2Organ level 3Organ level 4LevelPubmedSpeciesStageRna symbol
Endocrinethyroid   highly
Nervousbrain    
Respiratorylung   highly
cells
SystemCellPubmedSpeciesStageRna symbol
not specificchondrocyte Homo sapiens
cell lineage
cell lines
fluid/secretion
at STAGE
PROTEIN
PHYSICAL PROPERTIES
STRUCTURE
motifs/domains
  • N-terminal tetratricopeptide repeats (TPRs)
  • a JmjC catalytic domain
  • a C-terminal segment within which is embedded a Zn2+-coordinated GATA-like (GATAL) domain of novel topology that is flanked by alpha-helical segments that form a four-helix bundle
    • HOMOLOGY
    interspecies homolog to C.elegans cosmid D2021
    Homologene
    FAMILY
  • UTX family
  • JmjC family histone
    • CATEGORY unknown/unspecified
    SUBCELLULAR LOCALIZATION     intracellular
    intracellular,nucleus,nucleoplasm
    basic FUNCTION
  • having a potent histone demethylase activity but is expressed mainly in an inducible and cell-type restricted fashion (histone H3K27-specific demethylase)
  • expressed in macrophages in response to bacterial products and inflammatory cytokines
  • demethylating lys 27 on histone H3, leading to decreased levels of H3K27 and causing delocalization of polycomb proteins
  • may be involved in anterior-posterior development
  • histone demethylase controling differentiation in a self-renewing mammalian tissue
  • contributes to the control of gene expression in lipopolysaccharide-activated macrophages, and participates in the inflammatory transcriptional response induced by LPS stimulation in macrophages )
  • H3K27 demethylases, KDM6Band KDM6A, mediate a functional interaction between the lineage-defining T-box transcription factor family and a SMARCA4-containing SWI/SNF remodeling complex
  • has a required role in general chromatin remodeling that is independent from its H3K27 demethylase potential(
  • histone H3 Lys 27 (H3K27) demethylase KDM6B has been shown to play important roles in transcriptional regulation and cell differentiation
  • KDM4B and KDM6B promotes osteogenic differentiation of mesenchymal stem/stromal cells (MSCs)
  • H3K27 demethylation and specifically KDM6B and KDM6A catalytic activity are critical determinants of proinflammatory gene activation in human primary macrophages
  • histone demethylase promoting epithelial-mesenchymal transition
  • plays an important role in the transcriptional response to different signaling pathways
  • RNA polymerase II progression through H3K27me3-enriched gene bodies requires KDM6B histone demethylase
  • previously unrecognized role in cellular reprogramming and provide molecular insight into the mechanisms by which the KDM6B-PHF20 axis controls this process
  • embryonic ectoderm development (EED)and KDM6B coordinate the first mammalian cell lineage commitment to ensure embryo implantation
  • is required for mesoderm differentiation and cardiovascular lineage commitment
  • JMJD3 controls the spermatogonial compartment through the regulation of fragmentation of spermatogonial cysts and this mechanism may be involved in maintenance of diverse stem cell niches
  • is a histone demethylase, which specifically catalyzes the removal of trimethylation of histone H3 at lysine 27 (H3K27me3)
  • novel function for KDM6B in activity-regulated neuronal survival, suggesting that activity- and KDM6B-dependent regulation of inflammatory gene pathways may serve as an adaptive pro-survival response to increased neuronal activity
  • regulates target gene expression in the embryonic stages of lung development
  • early embryonic H3K27me3 repression can be alleviated in the absence of active demethylation by KDM6A, KDM6B
  • is an epigenetic factor in T-cell differentiation via changes in histone methylation and target gene expression
  • H3K27me3 demethylase that counteracts polycomb-mediated transcription repression
  • is a key epigenetic regulator in the process of cartilage maturation during endochondral bone formation
  • KDM6B and KDM6A are required for T-cell development, and point to a requirement for their H3K27Me3 demethylase activity in cell differentiation
  • significantly increased during cartilage development
  • role for KDM6B in the postmitotic stages of cerebellar granule neurons (CGNs) maturation
  • has an anti-tumorigenic function in neuroblastoma by promoting differentiation
  • potential role for KDM6B as a regulator of podocyte differentiation, which is important for the understanding of podocyte function in kidney development and related diseases
  • multifaceted role for KDM6B, placing it as a key partner of KLF4 and a scaffold that assists chromatin interactions and activates gene transcription
  • KDM6B can act as both a tumor suppressor and an oncogene depending on the cellular context
    • CELLULAR PROCESS
    PHYSIOLOGICAL PROCESS
    PATHWAY
    metabolism
    signaling
    a component
    INTERACTION
    DNA
    RNA
    small molecule metal binding,
  • binding Fe(II)
    • protein
  • binds Polycomb group target genes
  • interacting with HOXA11, which is a target in differentiating bone marrow cells (but in macrophages is an inactive gene with high and constant H3K27me3 levels during stimulation)
  • association with RBBP5-containing complexes
  • demethylation of H3K27me3 in the NFATC1 gene locus by KDM6B plays a critical role in TNFSF11-induced osteoclast differentiation
  • KDM6B and KDM7A play a role in localizing elongation factors SUPT6H and SUPT16H to the target genes
  • KDM6A and KDM6B contribute to the activation of WNT3 and DKK1 at different differentiation stages when WNT3 and DKK1 are required for mesendoderm and definitive endoderm differentiation, respectively
  • following commitment to megakaryocyte differentiation, the H3K27 demethylase KDM6B up-regulation influences both ITGA2B and MPL expression
  • regulates transcription of transforming growth factor beta (TGFbeta)-responsive genes by promoting RNA polymerase II (RNAPII) progression along the gene bodies
  • chromatin regulators EP300, KDM5A, KDM6A and KDM6B cooperate with KLF4 in promoting the transcription of POU5F1
  • KDM6B-targeting of PHF20 for ubiquitination and degradation via recruitment of an E3 ligase, TRIM26
  • plays important roles in osteoblast differentiation and regulates the expressions of IBSP and BGLAP via transcription factors RUNX2 and SP7
  • KDM6B associates with RUNX2 to promote proliferation and hypertrophy of chondrocytes
  • role of KDM6B as a novel inducer of senescence-associated heterochromatin foci (SAHF), formation through demethylating RB1
  • KDM6B promotes esophageal squamous cell carcinoma (ESCC) progression by increasing the transcriptional activity of CEBPB depending on its H3K27 demethylase activity
  • vital role of the ESR1/KDM6B regulatory axis in the epigenetic regulation of the estrogen-dependent osteogenic response
    • cell & other
    REGULATION
    induced by by inflammatory stimuli in macrophages
    TGFB1, and the knockdown of KDM6B inhibited EMT induced by TGFB1
    Other regulation by NF-kB
    ASSOCIATED DISORDERS
    corresponding disease(s) NEDCFSA
    Other morbid association(s)
    TypeGene ModificationChromosome rearrangementProtein expressionProtein Function
    tumoral     --over  
    in esophageal squamous cell carcinoma (ESCC) patients with lymph node metastasis
    tumoral     --low  
    in poorly differentiated high-risk neuroblastomas
    tumoral     --over  
    in differentiated tumors, and high KDM6B expression is prognostic for better survival in neuroblastoma patients
    Susceptibility
    Variant & Polymorphism
    Candidate gene
    Marker
  • low KDM6B was an independent predictor of poor prognosis in surgically resected colorectal cancer (CRC) patients
    • Therapy target
    SystemTypeDisorderPubmed
    immunologyautoimmune 
    KDM6B can be a novel therapeutic target for suppressing autoimmune responses
    osteoarticularboneostéoporosis
    KDM6B may present as therapeutic targets for controlling mesenchymal stem/stromal cells (MSCs) fate choices and lead to clues for new treatment in metabolic bone diseases such as osteoporosis
    cardiovascularatheroma 
    cell-specific pharmacologic therapy targeting KDM6B may be an effective intervention for Abdominal aortic aneurysms (AAAs) expansion
    cancerdigestivecolon
    potential new therapeutic targetapproach for CRC patients
    ANIMAL & CELL MODELS
  • Jmjd3-deficient mice were resistant to the induction of experimental autoimmune encephalomyelitis (EAE)