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FLASH GENE

Symbol

HDAC3

contributors: mct/ - updated : 10-04-2021

HGNC name	histone deacetylase 3
HGNC id	4854

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

Corresponding disease	IDEMS intellectual disability, epilepsy, and musculoskeletal abnormalities
Location	5q31.3      Physical location : 141.000.442 - 141.016.423
Synonym symbol(s)	HD3, RPD3, RPD3-2, SMAP45
EC.number	3.5.1.98

DNA

TYPE	functioning gene
STRUCTURE	15.98 kb     15 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen -D5S393 - D5S89 - D5S2429 - D5S399 - D5S479 - D5S1983 - D5S414 - D5S1701 - EGR1 - D5S500 - D5S476 - D5S1372 - D5S166 - D5S2414 - D5S2430 - D5S1867 - D5S2116 - CD14 - D5S1760 - D5S658 - D5S2424 - D5S1898 - D5S2119 - HDAC3 - D5S1541 - D5S2010 - D5S1979 - D5S2437 - D5S2481 - GRIA1 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_003883 15 - 1965 NP_003874 48.7 428 - 1998 PMID: 950116

EXPRESSION

Type	ubiquitous

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 Reproductive female system ovary     highly   female system uterus cervix   highly Skeleton           Homo sapiens Adult Skin/Tegument skin       highly

cells

System Cell Pubmed Species Stage Rna symbol Skeleton osteoblast Homo sapiens Adult

cell lineage

cell lines

fluid/secretion

at STAGE

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

HOMOLOGY

interspecies

ortholog to yeast Rpd3

Homologene

FAMILY	histone deacetylase family
	type 1 subfamily

CATEGORY

enzyme , transcription factor

SUBCELLULAR LOCALIZATION	extracellular
	intracellular
	intracellular,cytoplasm,cytoskeleton,microtubule
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	histone deacetyltransferase, modulator of chromatin structure
	responsible for the deacetylase activities that are associated with HDAC4 and HDAC7
	can function as the catalytic subunits of multiprotein complexes
	activation of HDAC3 by NCOR1 is a nodal point in the epigenetic regulation of circadian and metabolic physiology
	central role in regulating the cell proliferation and differentiation of colon cancer cells, suggesting a potential mechanism by which colon cancers may become resistant to luminal butyrate
	critical roles in S phase progression and DNA damage control
	concerted action of both HDAC3 and L3MBTL2 in histone deacetylation and methylation-dependent transcriptional repression
	functions in the regulation of circadian rhythm and glucose metabolism
	selectively represses CREB3-mediated transcriptional activation and chemotactic signaling in human metastatic breast cancer cells
	critical role for HDAC3 in the molecular mechanisms underlying long-term memory formation
	genome-wide diurnal recruitment of HDAC3 directs a rhythm of epigenomic modification, Pol II recruitment, and gene expression
	circadian NR1D1 recruitment of HDAC3 to lipid metabolic genes plays a critical physiological role
	NR1D1 colocalizes with HDAC3 near genes regulating lipid metabolism
	HDAC3 activity is necessary for osteoclast formation
	essential role for HDAC3, a chromatin modifier, in hypoxia-induced epithelial-mesenchymal transition (EMT)
	under hypoxia, HDAC3 interacts with hypoxia-induced WDR5, recruits the histone methyltransferase (HMT) complex to increase histone H3 lysine 4 (H3K4)-specific HMT activity, and activates mesenchymal gene expression
	plays a critical and specific regulatory role in the neural crest-derived smooth muscle lineage and in formation of the cardiac outflow tract
	IRF8, ETV6 and HDAC3 cooperated to increase sensitivity to FAS-induced apoptosis
	HDAC3 exerted a negative regulation on expression of HDAC2 via interaction with RAC1
	HDAC3 is involved in histone deacetylation of the IL12B promoter by IL10
	central role in inflammation, providing use of selective HDAC inhibitors as antiinflammatory agents
	nuclear enzyme that removes acetyl groups from lysine residues in histones and other proteins to epigenetically regulate gene expression
	its expression in osteoblasts and osteocytes is essential for bone maintenance during aging
	is essential to the mechanism by which RUNX2 represses AXIN2
	HDAC3 is able to regulate cyclin A degradation during mitosis via proteasome
	plays a critical role in cardiac progenitor cells to regulate early cardiogenesis
	HDAC3/DDX53 axis targets EGFR signaling and regulates the response to anti-cancer drugs
	is a crucial epigenetic modulator essential for various developmental and physiological functions
	complex role of HDAC3 in histone deacetylase activity, multi-protein complex interactions, and nuclear localization

CELLULAR PROCESS

nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	complexing with nuclear receptor corepressor NCOR2
	critical component of the N-CoR/SMRT repression complex
	core repression complex involves the recruitment of three proteins, HDAC3, GPS2 and TBL1X, to a highly conserved repression domain within NCOR2 and NCOR
	the formation of a stable and active HDAC3-corepressor complex is a stepwise process in which the C terminus of HDAC3 plays a critical role at late steps of the assembly process

INTERACTION

DNA

RNA

small molecule

protein	binding to YY1, involved in negative regulation of transcription
	interacting with KLF6 (potential mechanism underlying human adipogenesis)
	repressing DLK1
	interacting with NCOR1 (functions as an activating subunit for the chromatin modifying enzyme histone deacetylase 3 (HDAC3)
	interacting with SKI (SKI represses retinoic acid (RA) signaling by interacting with, and stabilizing, key components of the co-repressor complex, namely, HDAC3)
	KIAA1967 is an endogenous inhibitor of HDAC3 (interacts and specifically inhibits the deacetylase HDAC3)
	genomic recruitment of HDAC3 by NR1D1 directs a circadian rhythm of histone acetylation and gene expression required for normal hepatic lipid homeostasis
	EMD binds directly to HDAC3, the catalytic subunit of the nuclear co-repressor (NCoR) complex, and recruits HDAC3 to the nuclear periphery
	HDAC3 mediates allergic skin inflammation in relation with angiogenesis by regulating MS4A2
	HDAC3-RAC1 interaction, but not HDAC3 activity, is necessary for down-regulation of HDAC2 by RAC1
	was necessary for the induction of CCL2
	HDAC2, negatively regulated by MS4A2 and HDAC3, is under the control of proteasome-dependent ubiquitination
	association of HDAC3 and HDAC6 with JDP2 and ATF3 occurs via direct protein-protein interactions
	nuclear receptor co-repressors are required for HDAC3 enzyme activity in vivo and suggest that a deacetylase-independent function of HDAC3 may be required for life
	RUNX2, HDAC3, repress AXIN2 transcription in osteoblasts
	HDAC3 is necessary for ESR1 mRNA stability, and is involved in the estrogen-dependent proliferation of ESR1-positive tumors
	HDAC3 directly interacts with and deacetylates CCNA2
	HDAC3 regulates cyclin A stability by counteracting the action of the acetylases KAT2A/KAT2B
	interaction with NCOR2 is essential for deacetylase-independent function of HDAC3
	HDAC3 physically interacts with TBX5 and modulates its acetylation to repress TBX5-dependent activation of cardiomyocyte lineage-specific genes
	RBM15 which associates with HDAC3 and the histone methyltransferase, SETD1B, binds to both MPL RNA and chromatin and regulates H4 acetylation and H3K4me3 marks
	PDCD5 selectively mediates HDAC3 dissociation from TP53, which induces HDAC3 cleavage and ubiquitin-dependent proteasomal degradation
	PDCD5 competitively inhibited interaction between histone deacetylase 3 (HDAC3) and AKT1
	interaction between NKAP and HDAC3 is critical for T Cell maturation
	EMD regulation of HDAC3 activity to affect H4K5 acetylation dynamics is important for myogenic differentiation
	HDAC3 interacts with FOXK1, co-localizes with FOXK1 at the promoter of STAT1 and STAT2, and is required for protecting FOXK1 from lysosomal system-mediated degradation
	biological importance of HDAC3 in regulating the antiviral immunity of macrophages through interacting with FOXK1 to regulate the expression of STAT1 and STAT2

cell & other

REGULATION

induced by

HIF1A (HDAC3is essential for hypoxia-induced EMT and metastatic phenotypes)

ASSOCIATED DISORDERS

corresponding disease(s)

IDEMS

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral     --over   in squamous cell lung carcinomas

Susceptibility

Variant & Polymorphism

Candidate gene
Marker
Therapy target
	System Type Disorder Pubmed blood     HDAC3 inhibitors are being considered as promising candidates for cancer therapy blood     promising target for therapies aiming to expand hematopoietic stem cells neurology neurodegenerative   HDAC3 inhibitors being tested for relief of expansion-associated gene silencing may also suppress somatic expansions that contribute to disease progression allergy     HDAC3 serves as a target for development of allergy therapeutics.

ANIMAL & CELL MODELS

deletion of Hdac3 or Nr1d1 in mouse liver causes hepatic steatosis