InnateDB: Systems Biology of the Innate Immune Response

Homo sapiens Protein: CTCF

Summary

InnateDB Protein

IDBP-36982.6

Last Modified

2014-10-13 [Report errors or provide feedback]

Gene Symbol

CTCF

Protein Name

CCCTC-binding factor (zinc finger protein)

Synonyms

MRD21;

Species

Homo sapiens

Ensembl Protein

ENSP00000264010

InnateDB Gene

IDBG-36980 (CTCF)

Protein Structure

UniProt Annotation

Function

Chromatin binding factor that binds to DNA sequence specific sites. Involved in transcriptional regulation by binding to chromatin insulators and preventing interaction between promoter and nearby enhancers and silencers. Acts as transcriptional repressor binding to promoters of vertebrate MYC gene and BAG1 gene. Also binds to the PLK and PIM1 promoters. Acts as a transcriptional activator of APP. Regulates APOA1/C3/A4/A5 gene cluster and controls MHC class II gene expression. Plays an essential role in oocyte and preimplantation embryo development by activating or repressing transcription. Seems to act as tumor suppressor. Plays a critical role in the epigenetic regulation. Participates in the allele-specific gene expression at the imprinted IGF2/H19 gene locus. On the maternal allele, binding within the H19 imprinting control region (ICR) mediates maternally inherited higher-order chromatin conformation to restrict enhancer access to IGF2. Plays a critical role in gene silencing over considerable distances in the genome. Preferentially interacts with unmethylated DNA, preventing spreading of CpG methylation and maintaining methylation-free zones. Inversely, binding to target sites is prevented by CpG methylation. Plays a important role in chromatin remodeling. Can dimerize when it is bound to different DNA sequences, mediating long-range chromatin looping. Mediates interchromosomal association between IGF2/H19 and WSB1/NF1 and may direct distant DNA segments to a common transcription factory. Causes local loss of histone acetylation and gain of histone methylation in the beta-globin locus, without affecting transcription. When bound to chromatin, it provides an anchor point for nucleosomes positioning. Seems to be essential for homologous X-chromosome pairing. May participate with Tsix in establishing a regulatable epigenetic switch for X chromosome inactivation. May play a role in preventing the propagation of stable methylation at the escape genes from X- inactivation. Involved in sister chromatid cohesion. Associates with both centromeres and chromosomal arms during metaphase and required for cohesin localization to CTCF sites. Regulates asynchronous replication of IGF2/H19. {ECO:0000269PubMed:11743158, ECO:0000269PubMed:16815976, ECO:0000269PubMed:17827499, ECO:0000269PubMed:18347100, ECO:0000269PubMed:18413740, ECO:0000269PubMed:18550811, ECO:0000269PubMed:18654629, ECO:0000269PubMed:19322193, ECO:0000269PubMed:8649389, ECO:0000269PubMed:9591631}.

Subcellular Localization

Nucleus, nucleoplasm. Chromosome. Chromosome, centromere. Note=May translocate to the nucleolus upon cell differentiation. Associates with both centromeres and chromosomal arms during metaphase. Associates with the H19 ICR in mitotic chromosomes. May be preferentially excluded from heterochromatin during interphase.

Disease Associations

Mental retardation, autosomal dominant 21 (MRD21) [MIM:615502]: A disorder characterized by significantly below average general intellectual functioning associated with impairments in adaptive behavior and manifested during the developmental period. Additional MRD21 features include short stature, microcephaly, and developmental delay. {ECO:0000269PubMed:23746550}. Note=The disease is caused by mutations affecting the gene represented in this entry.

Tissue Specificity

Ubiquitous. Absent in primary spermatocytes. {ECO:0000269PubMed:9591631}.

Comments

Interactions

Number of Interactions

This gene and/or its encoded proteins are associated with 63 experimentally validated interaction(s) in this database.
They are also associated with 21 interaction(s) predicted by orthology.

Experimentally validated
Total	63 [view]
Protein-Protein	54 [view]
Protein-DNA	9 [view]
Protein-RNA	0
DNA-DNA	0
RNA-RNA	0
DNA-RNA	0

Predicted by orthology
Total	21 [view]

Gene Ontology

Molecular Function

Accession	GO Term
GO:0000978	RNA polymerase II core promoter proximal region sequence-specific DNA binding
GO:0001078	RNA polymerase II core promoter proximal region sequence-specific DNA binding transcription factor activity involved in negative regulation of transcription
GO:0003677	DNA binding
GO:0003682	chromatin binding
GO:0003700	sequence-specific DNA binding transcription factor activity
GO:0003714	transcription corepressor activity
GO:0005515	protein binding
GO:0008270	zinc ion binding
GO:0043035	chromatin insulator sequence binding
GO:0043565	sequence-specific DNA binding
GO:0044212	transcription regulatory region DNA binding
GO:0046872	metal ion binding

Biological Process

GO:0000122	negative regulation of transcription from RNA polymerase II promoter
GO:0006306	DNA methylation
GO:0006349	regulation of gene expression by genetic imprinting
GO:0006351	transcription, DNA-templated
GO:0006355	regulation of transcription, DNA-templated
GO:0007059	chromosome segregation
GO:0010216	maintenance of DNA methylation
GO:0010628	positive regulation of gene expression
GO:0010629	negative regulation of gene expression
GO:0016568	chromatin modification
GO:0016584	nucleosome positioning
GO:0031060	regulation of histone methylation
GO:0035065	regulation of histone acetylation
GO:0040029	regulation of gene expression, epigenetic
GO:0040030	regulation of molecular function, epigenetic
GO:0045087	innate immune response (InnateDB)
GO:0045892	negative regulation of transcription, DNA-templated
GO:0045893	positive regulation of transcription, DNA-templated
GO:0070602	regulation of centromeric sister chromatid cohesion