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Published on: November 22, 2019
TET1-mediated different transcriptional regulation in prostate cancer
Jianhua Feng1, Qiang Wang2, Guangwei Li1
1Urology Department of Longgang District Central Hospital Shenzhen City 518116, Guangdong Province, China.
Abstract:
The recent studies demonstrated that the global 5-hydroxymethylcytosine (5 hmC) level decreased in prostate cancer (PCa) involved the 5-methylcytosine (5 mC) hydroxymethylase, Ten-eleven translocation (TET)1 reduction. 5 hmC and TET1 were both revealed a dual function in bivalent domain associated with developmental regulators in embryonic stem cell model. However, the mechanism underlying the DNA methylation and hydroxymethylation change mediated by TET1 downregulation in PCa remains unclear. Herein, using BSP to assess the 5 mC level in promoters of ten specific marker gene in PCa, our results present that Cdh1, Gstp1, Pten, Apc, Runx3 and Mgmt are observed to be hypermethylated in promoters and lower expression while Cyr61, Sema3c and Ptgs2 are reversed patterns compared to the normal prostate tissues. Furthermore, using ChIP methods to investigate the H3K4me3 and H3K27me3 patterns in promoters, these four markers are all demonstrated to be associated with Polycomb-repressed characterization and upregulated in response to TET1/PRC2 reduction in PCa. Thus, our findings reveal a distinct activating and repressive function of TET1-mediated transcriptional regulation in prostate cancer.
Insights
Prostate cancer (PCa) shows decreased 5-hydroxymethylcytosine (5 hmC) linked to Ten-eleven translocation (TET)1 reduction. TET1 influences gene expression via DNA methylation and hydroxymethylation, impacting PCa development.
Area of Science:
- Epigenetics
- Cancer Biology
- Molecular Oncology
Background:
- Global 5-hydroxymethylcytosine (5 hmC) levels are reduced in prostate cancer (PCa).
- This decrease is associated with reduced activity of the DNA hydroxymethylase, Ten-eleven translocation (TET)1.
- TET1 has a known dual role in epigenetic regulation, particularly in embryonic stem cells.
Purpose of the Study:
- To elucidate the mechanism of DNA methylation and hydroxymethylation changes mediated by TET1 downregulation in PCa.
- To investigate the specific roles of TET1 in regulating gene expression in prostate cancer.
Main Methods:
- Bisulfite sequencing (BSP) was used to assess 5-methylcytosine (5 mC) levels in gene promoters.
- Chromatin immunoprecipitation (ChIP) was employed to analyze H3K4me3 and H3K27me3 patterns in promoters.
Main Results:
- Hypermethylation and reduced expression of Cdh1, Gstp1, Pten, Apc, Runx3, and Mgmt were observed in PCa.
- Conversely, Cyr61, Sema3c, and Ptgs2 showed hypomethylation and increased expression in PCa.
- Four marker genes exhibited Polycomb-repressed characteristics and were upregulated following TET1/PRC2 reduction in PCa.
Conclusions:
- TET1 plays a distinct role in transcriptional regulation in prostate cancer.
- TET1 mediates both activating and repressive functions, influencing gene expression patterns in PCa through epigenetic modifications.
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