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Repressing Gene Transcription by Redirecting Cellular Machinery with Chemical Epigenetic Modifiers
Published on: September 20, 2018
Repression of Akt3 gene transcription by the tumor suppressor RIZ1
Qingnan Liu1,2, Xiaotian Qu1, Xiaolei Xie1
1Center for Medical Genetics, School of Life Sciences, Central South University, Changsha, Hunan, China.
Abstract:
RIZ1 has been studied as a tumor suppressor and may play a role in metabolic diseases related to the Western style diet, such as cancer and obesity. The Akt pathway is known to play a role in both cancer and obesity, and a link between Akt and RIZ1 has also been found. To better understand the role of RIZ1 in obesity and cancer, we investigated how RIZ1 regulates the expression of Akt3. We found that overexpression of RIZ1 in HEK293 cells reduced the expression of Akt3 protein. Luciferase reporter activity of Akt3 gene promoter was significantly reduced in cells co-transfected with RIZ1. Recombinant proteins of RIZ1 was able to bind the Akt3 promoter in vitro, and chromatin immunoprecipitation assay also demonstrated the ability of RIZ1 binding to the Akt3 promoter in vivo. Overexpression of RIZ1 increased H3K9 methylation on the Akt3 promoter. These results identify Akt3 as a target of RIZ1 regulation and expand our understanding of the Akt pathway in cancer and obesity.
Insights
RIZ1 (PR domain zinc finger protein 1) acts as a tumor suppressor and regulates Akt3 expression. This research reveals RIZ1
Area of Science:
- Molecular Biology
- Cancer Research
- Metabolic Diseases
Background:
- RIZ1 is implicated as a tumor suppressor in metabolic diseases like obesity and cancer.
- The Akt pathway is crucial in both cancer and obesity, with a known link to RIZ1.
Purpose of the Study:
- To investigate the regulatory role of RIZ1 in the expression of Akt3.
- To elucidate the molecular mechanisms underlying RIZ1's influence on the Akt pathway in the context of cancer and obesity.
Main Methods:
- Overexpression of RIZ1 in HEK293 cells.
- Luciferase reporter assays to assess Akt3 promoter activity.
- In vitro binding assays with recombinant RIZ1 and the Akt3 promoter.
- Chromatin immunoprecipitation (ChIP) assays to confirm in vivo binding.
- Analysis of H3K9 methylation on the Akt3 promoter.
Main Results:
- Overexpression of RIZ1 led to reduced Akt3 protein levels.
- RIZ1 significantly repressed Akt3 gene promoter activity.
- RIZ1 directly binds to the Akt3 promoter both in vitro and in vivo.
- RIZ1 overexpression increased H3K9 methylation at the Akt3 promoter.
Conclusions:
- Akt3 is identified as a direct transcriptional target of RIZ1.
- RIZ1-mediated regulation of Akt3 contributes to understanding the Akt pathway in cancer and obesity.
- This study expands knowledge on RIZ1's function in metabolic and oncogenic processes.
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