English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Aim    p16  Methylation frequently occurs in carcinogenesis. While it has been hypothesized that the  p16  methylation states are dynamically maintained in cancer cells, direct evidence supporting this hypothesis has not been available until now.    Methods  A fusion cell model was established which reprogrammed the native DNA methylation pattern of the cells. The methylation status of the  p16  alleles was then repeatedly quantitatively analyzed in the fusion monoclonal, parental cancer cell lines ( p16 -completely methylated-AGS and unmethylated-MGC803), and HCT116 non-fusion cell using DHPLC and bisulfite sequencing. Histone methylation was analyzed using chromatin immuno-precipitation (ChIP)-PCR. P16 expression status was determined using immuno-staining and RT-PCR.    Results  The methylation status for the majority of the  p16  alleles was stably maintained in the fusion monoclonal cells after up to 60 passages. Most importantly, focal de novo methylation, demethylation, and hydroxymethylation were consistently observed within about 27% of the  p16  alleles in the fusion monoclones, but not the homozygously methylated or unmethylated parental cells. Furthermore, subclones of the monoclones consistently maintained the same  p16  methylation pattern. A similar phenomenon was also observed using the  p16  hemi-methylated HCT116 non-fusion cancer cell line. Interestingly, transcription was not observed in  p16  alleles that were hydroxymethylated with an antisense-strand-specific pattern. Also, the levels of H3K9 and H3K4 trimethylation in the fusion cells were found to be slightly lower than the parental AGS and MGC803 cells, respectively.    Conclusion  The present study provides the first direct evidence confirming that the methylation states of  p16  CpG islands is not only homeostatically maintained, but also accompanied by a dynamic process of transient focal methylation, demethylation, and hydroxymethylation in cancer cells.

Homeostatic Maintenance of Allele-Specific p16 Methylation in Cancer Cells Accompanied by Dynamic Focal Methylation and Hydroxymethylation