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FLASH GENE

Symbol

CHD8

contributors: mct/shn - updated : 15-11-2023

HGNC name	chromodomain helicase DNA binding protein 8
HGNC id	20153

FLASH GENE DNA RNA EXPRESSION PROTEIN DISORDER ANIMAL & CELL MODELS

DNA

TYPE	functioning gene
STRUCTURE	52.11 kb     38 Exon(s)

regulatory sequence

MAPPING

cloned

Y

linked

N

status

provisional

Map	cen - D14S1023 - D14S1070 - CHD8 - D14S1003 - D14S742 - qter

RNA

TRANSCRIPTS	type	messenger

identification nb exons type bp product Protein kDa AA specific expression Year Pubmed NM_020920 38 - 7499 NP_065971 240 2302 - 2023 37802044 NM_001170629 37 - 8254 NP_001164100 - 2581 - 2023 37802044

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 Lymphoid/Immune lymph node         Nervous brain         Respiratory lung

tissue

System Tissue Tissue level 1 Tissue level 2 Level Pubmed Species Stage Rna symbol Lymphoid

cell lineage

cell lines

fluid/secretion

at STAGE

physiological period

embryo

Text	expressed at a high level during early embryogenesis

PROTEIN

PHYSICAL PROPERTIES

STRUCTURE

motifs/domains

ATPase related SNF2 N terminal domain

HOMOLOGY

interspecies	ortholog to Chd8, Mus musculus
	ortholog to CHD8, Pan troglodytes
	ortholog to Chd8, Rattus norvegicus

Homologene

FAMILY	chromodomain helicase DNA-binding (CHD) family
	SNF2 superfamily of ATP-dependent chromatin remodellers

CATEGORY

regulatory , DNA associated , transcription factor

SUBCELLULAR LOCALIZATION	intracellular
	intracellular,nucleus,nucleoplasm
	intracellular,nucleus,chromatin/chromosome
text	translocated to the nucleus by interacting with importin alpha, and nuclear localization is essential for the function of Duplin

basic FUNCTION	is a negative regulator of the Wnt–â-catenin signaling pathway
	signaling pathway by affecting the downstream beta-catenin target genes
	CTCF-CHD8 complex has a role in insulation and epigenetic regulation at active insulator sites
	may possess antiapoptotic activity depending of Wnt signalling inhibition
	ATP-dependent chromatin remodeler that regulates the expression of many genes
	prevents apoptosis mediated by the tumour suppressor protein p53
	associates with ZNF143 and contributes to efficient U6 RNA polymerase III transcription
	may be functioning in transcription through the ATP-dependent modulation of chromatin structure
	alters HOXA2 gene expression and regulates the recruitment of chromatin modifying enzymes
	represses ATRA mediated HOXA2 gene expression
	essential role of CHD8 in E2F-dependent transcription activation
	CHD8 mediates cortical neurogenesis via transcriptional regulation of cell cycle and Wnt signaling
	key role for CHD8 in cerebellar development, with important implications for understanding the contribution of this brain region to autism spectrum disorder (ASD) pathogenesis
	transcriptional regulator that is expressed in nearly all cell types and has been implicated in multiple cellular processes, including cell cycle, cell adhesion, neuronal development, myelination, and synaptogenesis
	CHD8 plays an essential role in the pluripotency exit and neuroectoderm differentiation as well as the regulation of apoptosis during neurogenesis
	CHD8 is essential for erythroblast cytokinesis

CELLULAR PROCESS	cell life, antiapoptosis
	nucleotide, chromatin organization, remodeling
	nucleotide, transcription, regulation

PHYSIOLOGICAL PROCESS

PATHWAY

metabolism

signaling

a component	component of the chromatin remodeling complex
	role of CTCF-CHD8 complex in insulation and epigenetic regulation at active insulator sites
	part of a CHD8/WDR5/ASH2L/RBBP5 complex

INTERACTION

DNA

binding

RNA

small molecule

protein	p53 and Histone H1
	insulator-binding protein CTCF
	elongating RNA polymerase II (RNAPII) and controls expression of the cyclin E2 gene (CCNE2)
	associates with several proteins linked to chromatin modification, among them chromodomain-helicase-DNA binding protein 8 (CHD8)
	interacts directly with beta-catenin and is also recruited specifically to the promoter regions of several beta-catenin-responsive genes
	interacts with several proteins including the WAR complex
	CHD7 and CHD8 proteins are interacting directly and indirectly via additional linker proteins (loss of the direct CHD7–CHD8 interaction might change the conformation of a possible CHD7–CHD8 containing complex, which might be a disease mechanism in CHARGE syndrome)
	interacts directly with WDR5, a component of the histone H3 Lys-4 methyltransferase MLL complex
	FAM124B is a potential interacting partner of a CHD7 and CHD8 containing complex
	CHD8 binds E2F-dependent promoters at the G1/S transition but not in quiescent cells
	CHD8 is involved in late stages of progesterone receptor (PR) enhancers activation

cell & other

REGULATION

ASSOCIATED DISORDERS

corresponding disease(s)

Susceptibility

to Chiari I malformation (CM1)

Variant & Polymorphism other	de novo mutations in CHD8 among individuals with CM1

Candidate gene

Marker

Therapy target

ANIMAL & CELL MODELS

	Chd8–/– mouse embryos was arrested at gastrulation and died early during embryogenesis, manifesting widespread apoptosis, whereas deletion of p53 ameliorated this developmental arrest
	Chd8 +/- mice appeared normal and were fertile
	Complete loss of Chd8 causes embryonic lethality in mice as a result of TP53-mediated apoptosis