Редактирование: CBX5

Chromobox protein homolog 5 (Antigen p25) (Heterochromatin protein 1 homolog alpha) (HP1 alpha) [HP1A]

==Publications==

{{medline-entry
|title=The Ubiquitin-like with PHD and Ring Finger Domains 1 ([[UHRF1]])/DNA Methyltransferase 1 ([[DNMT1]]) Axis Is a Primary Regulator of Cell Senescence.
|pubmed-url=https://pubmed.ncbi.nlm.nih.gov/28100769
|abstract=As senescence develops, cells sequentially acquire diverse senescent phenotypes along with simultaneous multistage gene reprogramming. It remains unclear what acts as the key regulator of the collective changes in gene expression at initiation of senescent reprogramming. Here we analyzed time series gene expression profiles obtained in two different senescence models in human diploid fibroblasts: replicative senescence and H O -induced senescence. Our results demonstrate that suppression of DNA methyltransferase 1 ([[DNMT1]])-mediated DNA methylation activity was an initial event prior to the display of senescent phenotypes. We identified seven [[DNMT1]]-interacting proteins, ubiquitin-like with PHD and ring finger domains 1 ([[UHRF1]]), [[EZH2]], [[CHEK1]], [[SUV39H1]], [[CBX5]], [[PARP1]], and [[HELLS]] (also known as LSH (lymphoid-specific helicase) 1), as being commonly down-regulated at the same time point as [[DNMT1]] in both senescence models. Knockdown experiments revealed that, among the [[DNMT1]]-interacting proteins, only [[UHRF1]] knockdown suppressed [[DNMT1]] transcription. However, [[UHRF1]] overexpression alone did not induce [[DNMT1]] expression, indicating that [[UHRF1]] was essential but not sufficient for [[DNMT1]] transcription. Although [[UHRF1]] knockdown effectively induced senescence, this was significantly attenuated by [[DNMT1]] overexpression, clearly implicating the [[UHRF1]]/[[DNMT1]] axis in senescence. Bioinformatics analysis further identified [[WNT5A]] as a downstream effector of [[UHRF1]]/[[DNMT1]]-mediated senescence. Senescence-associated hypomethylation was found at base pairs -1569 to -1363 from the transcription start site of the [[WNT5A]] gene in senescent human diploid fibroblasts. As expected, [[WNT5A]] overexpression induced senescent phenotypes. Overall, our results indicate that decreased [[UHRF1]] expression is a key initial event in the suppression of [[DNMT1]]-mediated DNA methylation and in the consequent induction of senescence via increasing [[WNT5A]] expression.
|mesh-terms=* CCAAT-Enhancer-Binding Proteins
* Cellular Senescence
* DNA (Cytosine-5-)-Methyltransferase 1
* DNA (Cytosine-5-)-Methyltransferases
* DNA Methylation
* Fibroblasts
* Gene Expression Profiling
* Gene Expression Regulation
* HEK293 Cells
* Histones
* Humans
* Hydrogen Peroxide
* Male
* Oligonucleotide Array Sequence Analysis
* Phenotype
* Promoter Regions, Genetic
* Protein Binding
* Protein Domains
* RNA, Small Interfering
* Ubiquitin-Protein Ligases
* Wnt-5a Protein
* beta-Galactosidase
|keywords=* DNA methylation
* cellular senescence
* gene expression
* gene regulation
* microarray
|full-text-url=https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5339756
}}