CBX7 (chromobox homolog 7)

Alias_names	chromobox 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.

	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.

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.

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