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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
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)