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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

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	20.58 kb     22 Exon(s)

MAPPING

cloned

Y

linked

status

confirmed

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_001080424 22 - 6704 NP_001073893 - 1682 - 2007 18003914 NM_001348716 24 - 6728 NP_001335645 - 1643 - 2007 18003914

EXPRESSION

Type

widely

expressed in	(based on citations)
organ(s)	System Organ level 1 Organ level 2 Organ level 3 Organ level 4 Level Pubmed Species Stage Rna symbol Endocrine thyroid       highly Nervous brain         Respiratory lung       highly

cells

System Cell Pubmed Species Stage Rna symbol not specific chondrocyte 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)

Type Gene Modification Chromosome rearrangement Protein expression Protein 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
	System Type Disorder Pubmed immunology autoimmune   KDM6B can be a novel therapeutic target for suppressing autoimmune responses osteoarticular bone ostéoporosis 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 cardiovascular atheroma   cell-specific pharmacologic therapy targeting KDM6B may be an effective intervention for Abdominal aortic aneurysms (AAAs) expansion cancer digestive colon potential new therapeutic targetapproach for CRC patients

ANIMAL & CELL MODELS

Jmjd3-deficient mice were resistant to the induction of experimental autoimmune encephalomyelitis (EAE)