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CBX7 (chromobox homolog 7)

Written2011-11Ana O'Loghlen, Jesus Gil
Cell Proliferation Group, MRC Clinical Sciences Centre, Imperial College London, Hammersmith Campus, London W12 0NN, UK

(Note : for Links provided by Atlas : click)

Identity

Alias_nameschromobox homolog 7
Other alias
HGNC (Hugo) CBX7
LocusID (NCBI) 23492
Atlas_Id 43845
Location 22q13.1  [Link to chromosome band 22q13]
Location_base_pair Starts at 39130774 and ends at 39152650 bp from pter ( according to hg19-Feb_2009)  [Mapping CBX7.png]
 
  Figure 1. Location of Cbx7 within Chromosome 22.
Fusion genes
(updated 2016)
CBX7 (22q13.1) / VPREB1 (22q11.22)
Note Orientation: minus strand. Size: 32508 bases.

DNA/RNA

 
  Figure 2. Diagram of Cbx7 transcript. Cbx7 has 6 exons. The black boxes indicate the consensus coding sequences (CCDS).
Description DNA size is 4081 bp with 6 exons. CBX7 is a highly conserved gene in chimpanzee, dog, cow, rat and mouse.
Transcription mRNA size: 3964 bp.

Protein

Note 251 amino acids.
Isoelectric point: 10,0228.
Molecular weight of the protein: 28209 Da.
 
  Figure 3. Structure of Cbx7 protein. Cbx7 has a chromodomain motif and a Polycomb (Pc) box which are indicated in grey.
Description CBX7 has a chromodomain region which is commonly found in proteins associated with the remodelling and manipulation of chromatin. In mammals, chromodomain-containing proteins are responsible for aspects of gene regulation related to chromatin remodelling and formation of heterochromatin regions. Chromodomain-containing proteins also bind methylated histones and appear in the RNA-induced transcriptional silencing complex. Specifically, CBX7 is involved in maintaining the transcriptionally repressive state of its target genes. The better characterized target of CBX7 is the INK4a/ARF locus, which is repressed by CBX7 in order to overcome the senescent phenotype in several mouse and human cell lines. Repression of other targets like E-cadherin has been also suggested.
Expression CBX7 is expressed ubiquitously, but at higher levels in the nervous system, thyroid gland, prostate, fallopian tubes and bladder in normal tissue. CBX7 expression is also high in ES cells.
Localisation In the nucleus.
Function CBX7 is a member of the Polycomb group (PcG) genes, which are transcriptional repressors that play an essential role in development, cancer progression and stem cell maintenance. Mainly two different PcG complexes have been described: Polycomb Repressive Complex 1 (PRC1) and PRC2. PRC2 is the complex implicated in initiating the silencing of its target genes by methylating histone H3 on lysines 9 and 27. PRC1 is implicated in stabilizing this repressive state by recognizing the methylation marks through the Polycomb proteins and by ubiquitinating the histone H2A on Lys119. CBX7 belongs to the PRC1 complex and has been described to be a regulator of cellular lifespan by repressing the INK4a/ARF locus in several mouse and human cell lines. On the other hand, depletion of CBX7 from the cell induces a senescent phenotype by increasing the expression of the cell cycle regulators p16/ARF.
X chromosome inactivation
CBX7 has high affinity for binding H3K9me3 and H3K27me3. It associates with heterochromatin, binds RNA and it's enriched in the X chromosome, giving CBX7 a role in maintaining the repression of genes in the X chromosome.
Epigenetic regulation
CBX7, as part of the PRC1 complex, has a role in maintaining the repressive state of its target genes. CBX7 binds to the long non-coding RNA ANRIL in order to represses the INK4a/ARF locus and this interaction is essential for CBX7's function. Both CBX7 and ANRIL have been found to have high levels in prostate cancer tissues.
Stem cells self-renewal
CBX7 has been recently implicated to be essential for maintaining the pluripotency state of stem cells (ES cells). Overexpression of CBX7 in ESC impairs cell differentation. On the other hand, depletion of CBX7 from ESC induces spontaneous differentiation. Two different miR families (miR-125 and miR-181) were identified in a screening for CBX7 regulators and have been described to have a role in ESC differentiation by targeting the 3'UTR of CBX7.
 
  Figure 4. 4a: Summary of Cbx7's mechanism in embryonic stem cells (ESC). Cbx7 is essential for ESC self-renewal. Loss of Cbx7, either by differentiating ESC or by an exogenous/endogenous induction of the microRNA (miR) families miR-125 and miR-181, induces ESC differentiation. This is accompanied by an increase in other Cbxs as they are targets of Cbx7. On the other hand, overexpression of Cbx7 in ESC reinforces pluripotency and keeps the cells in an ESC-like state when forced to differentiate. 4b and 4c: Summary of Cbx7's mechanism in human primary fibroblasts (IMR-90). Ectopic expression of the miR families miR-125 and miR-181 induces a degradation of Cbx7 mRNA in IMR-90. Depletion of Cbx7 induces the cells to senesce. Thus, overexpression of miR-125 and miR-181 induces senescence through downregulation of Cbx7.

Mutations

Note Expression of CBX7 without the Pc box or with point mutations in the chromodomain region (F11A, K31A, W32A, W35A) does not extend the life span of human or mouse cells. The mutant R17Q, which affects the binding of CBX7 to RNA, extended the lifespan of cells, but to a lesser extent than CBX7 wt. Point mutations in the Pc box as F234D or F244D result in loss or reduced interaction of CBX7 with RNF2.

Implicated in

Note
  
Entity Various cancers
Disease CBX7 has been implicated in several tumors such as gastric cancer, follicular lymphoma, breast cancer, colon carcinoma, pancreatic cancer, tyroid cancer, glioma.
Prognosis There is a controversy in the role of CBX7 in cancer, as some papers associate CBX7 overexpression with poor prognosis and advanced estate of the tumor and aggressiveness, while others state that depletion of CBX7 from certain cancers indicates the state of malignancy of the tumor. The ability of CBX7 to regulate multiple targets and the relevance of those targets in different tumor types and stages probably explain those paradoxical findings.
  

Bibliography

CBX7 controls the growth of normal and tumor-derived prostate cells by repressing the Ink4a/Arf locus.
Bernard D, Martinez-Leal JF, Rizzo S, Martinez D, Hudson D, Visakorpi T, Peters G, Carnero A, Beach D, Gil J.
Oncogene. 2005 Aug 25;24(36):5543-51.
PMID 15897876
 
Mouse polycomb proteins bind differentially to methylated histone H3 and RNA and are enriched in facultative heterochromatin.
Bernstein E, Duncan EM, Masui O, Gil J, Heard E, Allis CD.
Mol Cell Biol. 2006 Apr;26(7):2560-9.
PMID 16537902
 
Role of polycomb group proteins in stem cell self-renewal and cancer.
Gil J, Bernard D, Peters G.
DNA Cell Biol. 2005 Feb;24(2):117-25. (REVIEW)
PMID 15699631
 
Nonoverlapping functions of the polycomb group cbx family of proteins in embryonic stem cells.
Morey L, Pascual G, Cozzuto L, Roma G, Wutz A, Benitah SA, Di Croce L.
Cell Stem Cell. 2012 Jan 6;10(1):47-62.
PMID 22226355
 
MicroRNA Regulation of Cbx7 Mediates a Switch of Polycomb Orthologs during ESC Differentiation.
O'Loghlen A, Munoz-Cabello AM, Gaspar-Maia A, Wu HA, Banito A, Kunowska N, Racek T, Pemberton HN, Beolchi P, Lavial F, Masui O, Vermeulen M, Carroll T, Graumann J, Heard E, Dillon N, Azuara V, Snijders AP, Peters G, Bernstein E, Gil J.
Cell Stem Cell. 2012 Jan 6;10(1):33-46.
PMID 22226354
 
Loss of the CBX7 gene expression correlates with a highly malignant phenotype in thyroid cancer.
Pallante P, Federico A, Berlingieri MT, Bianco M, Ferraro A, Forzati F, Iaccarino A, Russo M, Pierantoni GM, Leone V, Sacchetti S, Troncone G, Santoro M, Fusco A.
Cancer Res. 2008 Aug 15;68(16):6770-8.
PMID 18701502
 
Role of the chromobox protein CBX7 in lymphomagenesis.
Scott CL, Gil J, Hernando E, Teruya-Feldstein J, Narita M, Martinez D, Visakorpi T, Mu D, Cordon-Cardo C, Peters G, Beach D, Lowe SW.
Proc Natl Acad Sci U S A. 2007 Mar 27;104(13):5389-94. Epub 2007 Mar 20.
PMID 17374722
 
Molecular interplay of the noncoding RNA ANRIL and methylated histone H3 lysine 27 by polycomb CBX7 in transcriptional silencing of INK4a.
Yap KL, Li S, Munoz-Cabello AM, Raguz S, Zeng L, Mujtaba S, Gil J, Walsh MJ, Zhou MM.
Mol Cell. 2010 Jun 11;38(5):662-74.
PMID 20541999
 

Citation

This paper should be referenced as such :
O'Loghlen, A ; Gil, J
CBX7 (chromobox homolog 7)
Atlas Genet Cytogenet Oncol Haematol. 2012;16(3):220-222.
Free journal version : [ pdf ]   [ DOI ]
On line version : http://AtlasGeneticsOncology.org/Genes/CBX7ID43845ch22q13.html


External links

Nomenclature
HGNC (Hugo)CBX7   1557
Cards
AtlasCBX7ID43845ch22q13
Entrez_Gene (NCBI)CBX7  23492  chromobox 7
Aliases
GeneCards (Weizmann)CBX7
Ensembl hg19 (Hinxton)ENSG00000100307 [Gene_View]
Ensembl hg38 (Hinxton)ENSG00000100307 [Gene_View]  chr22:39130774-39152650 [Contig_View]  CBX7 [Vega]
ICGC DataPortalENSG00000100307
TCGA cBioPortalCBX7
AceView (NCBI)CBX7
Genatlas (Paris)CBX7
WikiGenes23492
SOURCE (Princeton)CBX7
Genetics Home Reference (NIH)CBX7
Genomic and cartography
GoldenPath hg38 (UCSC)CBX7  -     chr22:39130774-39152650 -  22q13.1   [Description]    (hg38-Dec_2013)
GoldenPath hg19 (UCSC)CBX7  -     22q13.1   [Description]    (hg19-Feb_2009)
EnsemblCBX7 - 22q13.1 [CytoView hg19]  CBX7 - 22q13.1 [CytoView hg38]
Mapping of homologs : NCBICBX7 [Mapview hg19]  CBX7 [Mapview hg38]
OMIM608457   
Gene and transcription
Genbank (Entrez)AK124408 BC051773 BC128418 BU584870 BU584877
RefSeq transcript (Entrez)NM_001346743 NM_001346744 NM_175709
RefSeq genomic (Entrez)
Consensus coding sequences : CCDS (NCBI)CBX7
Cluster EST : UnigeneHs.356416 [ NCBI ]
CGAP (NCI)Hs.356416
Alternative Splicing GalleryENSG00000100307
Gene ExpressionCBX7 [ NCBI-GEO ]   CBX7 [ EBI - ARRAY_EXPRESS ]   CBX7 [ SEEK ]   CBX7 [ MEM ]
Gene Expression Viewer (FireBrowse)CBX7 [ Firebrowse - Broad ]
SOURCE (Princeton)Expression in : [Datasets]   [Normal Tissue Atlas]  [carcinoma Classsification]  [NCI60]
GenevisibleExpression in : [tissues]  [cell-lines]  [cancer]  [perturbations]  
BioGPS (Tissue expression)23492
GTEX Portal (Tissue expression)CBX7
Protein : pattern, domain, 3D structure
UniProt/SwissProtO95931   [function]  [subcellular_location]  [family_and_domains]  [pathology_and_biotech]  [ptm_processing]  [expression]  [interaction]
NextProtO95931  [Sequence]  [Exons]  [Medical]  [Publications]
With graphics : InterProO95931
Splice isoforms : SwissVarO95931
PhosPhoSitePlusO95931
Domaine pattern : Prosite (Expaxy)CHROMO_1 (PS00598)    CHROMO_2 (PS50013)   
Domains : Interpro (EBI)CBX7_C    Chromo/chromo_shadow_dom    Chromo_dom_subgr    Chromo_domain    Chromodomain-like    Chromodomain_CS   
Domain families : Pfam (Sanger)CBX7_C (PF17218)    Chromo (PF00385)   
Domain families : Pfam (NCBI)pfam17218    pfam00385   
Domain families : Smart (EMBL)CHROMO (SM00298)  
Conserved Domain (NCBI)CBX7
DMDM Disease mutations23492
Blocks (Seattle)CBX7
PDB (SRS)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
PDB (PDBSum)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
PDB (IMB)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
PDB (RSDB)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
Structural Biology KnowledgeBase2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
SCOP (Structural Classification of Proteins)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
CATH (Classification of proteins structures)2K1B    2L12    2L1B    3GS2    4MN3    5EPJ   
SuperfamilyO95931
Human Protein AtlasENSG00000100307
Peptide AtlasO95931
HPRD12234
IPIIPI00001385   IPI00921336   IPI00607599   IPI00878964   
Protein Interaction databases
DIP (DOE-UCLA)O95931
IntAct (EBI)O95931
FunCoupENSG00000100307
BioGRIDCBX7
STRING (EMBL)CBX7
ZODIACCBX7
Ontologies - Pathways
QuickGOO95931
Ontology : AmiGOnegative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  covalent chromatin modification  PcG protein complex  PRC1 complex  
Ontology : EGO-EBInegative regulation of transcription from RNA polymerase II promoter  nuclear chromatin  protein binding  nucleus  nucleoplasm  cytosol  transcription, DNA-templated  covalent chromatin modification  PcG protein complex  PRC1 complex  
NDEx NetworkCBX7
Atlas of Cancer Signalling NetworkCBX7
Wikipedia pathwaysCBX7
Orthology - Evolution
OrthoDB23492
GeneTree (enSembl)ENSG00000100307
Phylogenetic Trees/Animal Genes : TreeFamCBX7
HOVERGENO95931
HOGENOMO95931
Homologs : HomoloGeneCBX7
Homology/Alignments : Family Browser (UCSC)CBX7
Gene fusions - Rearrangements
Fusion : MitelmanCBX7/VPREB1 [22q13.1/22q11.22]  
Fusion: TCGACBX7 22q13.1 VPREB1 22q11.22 HNSC
Polymorphisms : SNP and Copy number variants
NCBI Variation ViewerCBX7 [hg38]
dbSNP Single Nucleotide Polymorphism (NCBI)CBX7
dbVarCBX7
ClinVarCBX7
1000_GenomesCBX7 
Exome Variant ServerCBX7
ExAC (Exome Aggregation Consortium)CBX7 (select the gene name)
Genetic variants : HAPMAP23492
Genomic Variants (DGV)CBX7 [DGVbeta]
DECIPHERCBX7 [patients]   [syndromes]   [variants]   [genes]  
CONAN: Copy Number AnalysisCBX7 
Mutations
ICGC Data PortalCBX7 
TCGA Data PortalCBX7 
Broad Tumor PortalCBX7
OASIS PortalCBX7 [ Somatic mutations - Copy number]
Somatic Mutations in Cancer : COSMICCBX7  [overview]  [genome browser]  [tissue]  [distribution]  
Mutations and Diseases : HGMDCBX7
LOVD (Leiden Open Variation Database)Whole genome datasets
LOVD (Leiden Open Variation Database)LOVD 3.0 shared installation
BioMutasearch CBX7
DgiDB (Drug Gene Interaction Database)CBX7
DoCM (Curated mutations)CBX7 (select the gene name)
CIViC (Clinical Interpretations of Variants in Cancer)CBX7 (select a term)
intoGenCBX7
NCG5 (London)CBX7
Cancer3DCBX7(select the gene name)
Impact of mutations[PolyPhen2] [SIFT Human Coding SNP] [Buck Institute : MutDB] [Mutation Assessor] [Mutanalyser]
Diseases
OMIM608457   
Orphanet
MedgenCBX7
Genetic Testing Registry CBX7
NextProtO95931 [Medical]
TSGene23492
GENETestsCBX7
Target ValidationCBX7
Huge Navigator CBX7 [HugePedia]
snp3D : Map Gene to Disease23492
BioCentury BCIQCBX7
ClinGenCBX7
Clinical trials, drugs, therapy
Chemical/Protein Interactions : CTD23492
Chemical/Pharm GKB GenePA26132
Clinical trialCBX7
Miscellaneous
canSAR (ICR)CBX7 (select the gene name)
Probes
Litterature
PubMed41 Pubmed reference(s) in Entrez
GeneRIFsGene References Into Functions (Entrez)
CoreMineCBX7
EVEXCBX7
GoPubMedCBX7
iHOPCBX7
REVIEW articlesautomatic search in PubMed
Last year publicationsautomatic search in PubMed

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