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FLASH GENE

Symbol

OLIG2

contributors: shn/mct - updated : 30-01-2024

HGNC name	oligodendrocyte lineage transcription factor 2
HGNC id	9398

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	3.26 kb     2 Exon(s)

10 Kb 5' upstream gene genomic sequence study

MAPPING

cloned

Y

linked

N

status

confirmed

Map	cen - D21S261 - D21S262 - OLIG2 - D21S1898 - D21S1910 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_005806 2 - 2505 NP_005797 - 323 oligodendroglial tumors of the brain, pMN domain of the spinal cord - 11955447

EXPRESSION

Type	restricted

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 Nervous brain         Homo sapiens   brain         Homo sapiens Adult   brain         Homo sapiens Fetal   spinal cord       specific

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Nervous central       Homo sapiens

cells

System Cell Pubmed Species Stage Rna symbol Nervous neuroectodermal cell Homo sapiens Nervous oligodendrocyte Homo sapiens Visual amacrine cell Homo sapiens Fetal Visual cone photoreceptor Homo sapiens Fetal Visual Muller cell Homo sapiens Fetal

cell lineage	gliogenic progenitors in the postnatal subventricular zone
cell lines	embryonic and adult NG2 cells
fluid/secretion

at STAGE

physiological period

embryo

Text	developing astrocytes

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains	in the N-terminus a triple serine motif phosphorylated in cycling neural progenitors but not in their differentiated progeny
	helix-loop-helix (HLH) DNA binding domain

conjugated

HOMOLOGY

interspecies	ortholog to Olig 2, Rattus norvegicus
	ortholog to Olig 2, Mus musculus
	ortholog to olig2, danio rerio
	ortholog to OLIG2, Pan troglodytes

Homologene

FAMILY

basic helix loop helix (BHLH) family of transcription family

CATEGORY

transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,cytoplasm
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome

basic FUNCTION	plays in cooperation with Neurogenin2 vital roles in the coordinated induction of pan-neuronal and subtype-specific properties of motoneurons
	required for oligodendrocytes and motor neuron specification in the spinal cord
	controlling the development of neural crest cells, astrocytes and oligodendrocytes, three neuroectodermal-derived cells
	plays critical roles in oligodendrocyte and motor neuron development
	export of OLIG2, stimulated AKT, by from the nucleus of neural stem cell is essential for the astrocyte differentiation
	required for the production of motor neurons and oligodendrocytes
	repressor of neurogenesis in cells reacting to brain injury and open innovative perspectives toward evoking endogenous neuronal repair
	having repressor function, both sufficient and necessary to prevent neuronal differentiation and to direct subventricular zone progenitors toward astrocytic and oligodendrocytic fates
	required for proliferation of neural progenitors and for glioma formation
	playing a crucial role in white matter astrocyte development, but not in the cortical gray matter astrocytes
	role in gliogenesis in the dorsal pallium
	play a role in ventral telencephalic neurogenesis
	marks a subpopulation of retinal progenitor cells (RPCs) that are biased toward the production of postmitotic progeny
	required for oligodendrocyte specification and differentiation
	has the ability to permeate the cell membrane without the addition of a protein transduction domain (PTD), similar to other basic helix-loop-helix transcription factors such as MYOD1 and NEUROD2
	OLIG2 itself had a transduction ability similar to other bHLH transcription factors
	functions as a prepatterning factor to direct SMARCA4 to oligodendrocyte-specific enhancers
	basic helix-loop-helix transcription factor necessary for oligodendroglial development and expressed continuously throughout the lineage
	is involved in correct formation of the prethalamus, which leads to exclusion of the EPHA3-expressing region and is crucial for proper thalamocortical axons (TCAs) formation
	plays a pivotal role in glioma development
	plays a crucial role in the neurogenesis of both spinal cord and brain
	OLIG2 is an onco-requisite factor in diffuse intrinsic pontine glioma (DIPG)
	OLIG2-lineage astrocytes are likely involved in inhibitory neuronal transmission
	novel function of OLIG2 in the periphery nervous system to regulate the terminal differentiation and maturation of olfactory sensory neurons
	is an important transcription factor essential for the specification and differentiation of oligodendrocytes as well as astrocytes and neurons during developmental stages
	functional roles of OLIG1 and OLIG2 in directing neuronal and glial formation during different stages in development
	is a transcription factor that activates the expression of myelin-associated genes in the oligodendrocyte-lineage cells
	OLIG2 is likely essential for anterior commissure formation, likely by regulating multiple biological processes

CELLULAR PROCESS

nucleotide, transcription

PHYSIOLOGICAL PROCESS

development , nervous system , neurogenesis

PATHWAY

metabolism

signaling

a component	likely phosphorylated OLIG2 proteins form stable homodimers, whereas unphosphorylated OLIG2 prefers to form heterodimers with other bHLH proteins such as NEUROG2
	OLIG2-SETDB1 complex can mediate transcriptional repression in oligodendrocytes progenitor cells (OPCs), affecting myelination

INTERACTION

DNA

RNA

small molecule

protein	NK2 homeobox 2, Nkx2.2
	SRY (sex determining region Y)-box 10, SOX10 and SOXE
	NEUROG2 to modulate gene expression in motor neuron progenitor cells
	ID2 (inhibited posttranslationally through the interaction with ID2)
	SMARCA4 is an integral component of the transcriptional control of myelination via interaction with OLIG2 at the onset of oligodendrocyte progenitor cells differentiation
	stage-specific regulatory role for OLIG2, mediated by OLIG1 that conveys opposing functions on the differentiation and maturation of oligodendrocytes
	LGR5 is regulated by OLIG2, which is important for both neurogenesis and stem-like cells in glioblastoma (GSCs) maintenance
	TAF9B binds to both promoters and distal enhancers of neuronal genes, partially co-localizing at binding sites of OLIG2, a key activator of motor neuron differentiation
	PROX1 is a transcription repressor and downstream target of proneural genes, that suppresses OLIG2 expression and therefore controls ventral spinal cord patterning
	SEH1L regulates oligodendrocyte progenitor cells (OPCs) differentiation by assembling OLIG2 and BRD7 into a transcription complex at nuclear periphery
	WNT signaling suppresses oligodendrogenesis via NEUROG2-dependent direct inhibition of OLIG2 expression

cell & other

REGULATION

Other	phosphorylation regulates OLIG2 cofactor choice and the motor neuron-oligodendrocyte fate switch
	proliferative function of OLIG2 is controlled by developmentally regulated phosphorylation of a conserved triple serine motif within the N-terminal domain
	OLIG2 SUMOylation enhances its genetic targeting ability, which in turn occludes TP53 recruitment to CDKN1A promoter for DNA-damage responses

ASSOCIATED DISORDERS

corresponding disease(s)

Other morbid association(s)

Type Gene Modification Chromosome rearrangement Protein expression Protein Function tumoral       gain of function activated in T cell lymphoblastic leukemia with t(14;21) (q11.2;q22) constitutional     --over   acute and chronic brain injury tumoral     --low   may be related to the malignant behavior of human glioblastoma tumoral     --over   in oligodendroglial tumors constitutional   amplification     Olig1 and Olig2 triplication causes developmental brain defects in Down syndrome constitutional     --over   over-expression inhibits neural progenitor proliferation through changes in potassium channel activity, thereby contributing to the reduced neuronal numbers and brain size in Down syndrome constitutional   deletion     in the cerebellum, deletion of both OLIG2 and OLIG1 results in impaired genesis of Purkinje cells (PCs) and Pax2(+) interneurons tumoral     --over   in diffuse intrinsic pontine glioma (DIPG)

Susceptibility

to schizophrenia

Variant & Polymorphism SNP	SNP rs762178 in OLIG2 seems to be a potential candidate in altering risk for schizophrenia in the Chinese Han population

Candidate gene
Marker	a molecular marker for human glial brain tumors
	a marker for the diagnosis of oligodendroglial tumours
Therapy target
	System Type Disorder Pubmed cancer brain   likely target gene as novel candidates in diffuse intrinsic pontine glioma (DIPG) therapy

ANIMAL & CELL MODELS

	in Olig1(-/-)2(-/-) double-mutant mice motoneurons are largely eliminated, and oligodendrocyte differentiation is abolished
	mice lacking Olig2 function demonstrates a failure of NG2 cell development at embryonic and perinatal stages
	in Olig2 deficient mouse, astrocyte development was retarded in the dorsal neocortex, but not in the basal forebrain
	Olig2 is triplicated and overexpressed in the Ts65Dn mouse (mouse models of Down syndrome) forebrain displaying cognitive deficits