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      Investigation of Epigenetic Control of DAX-1 Expression in Human Cell Lines

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      , BA, , PhD
      Journal of the Endocrine Society
      Oxford University Press

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          Abstract

          Dosage-Sensitive Sex Reversal, Adrenal Hypoplasia Congenita, Critical Region on the X chromosome, gene 1 ( DAX-1 or NR0B1) is an orphan nuclear hormone receptor implicated in Adrenal Hypoplasia Congenita (AHC) and Dosage Sensitive Sex Reversal (DSS). In both instances, DAX-1 plays a key role in growth and development by modulating hormone function. In DSS, mutations on the X-chromosome lead to duplication of the region containing DAX-1, resulting in sex reversal, and in AHC, mutations in the DAX-1 gene diminish development of adrenal tissue which leads to a reduction in adrenal hormone production. Expressed predominantly in tissues such as the testes, ovaries, breast, adrenal cortex, and lung, DAX-1 may serve as an indicator of aberrant growth. Here we hypothesize that DAX-1 is epigenetically regulated, specifically in cancer cells, thereby reducing its expression. We surveyed various human cancer cells in order to determine whether inhibiting DNA methylating enzymes released epigenetic control of the DAX-1 gene, resulting in an increase in expression. By implementing molecular techniques, such as bisulfite sequencing, we determined the precise methylation sites in the DAX-1 gene. Additionally, we carried out methylation specific restriction enzyme analysis to differentiate degrees of methylation between lung, breast, liver, cervical, and adrenal carcinoma cell lines. Following confirmation of the precise methylation sites, we utilized chromatin immunoprecipitation (ChIP) in order to identify the modifying proteins present on the DAX-1 CpG islands. In conjunction with these experimental techniques, we implemented a bioinformatics approach to analyze methylation in the promoter region of the DAX-1 gene across tissue sample data acquired from The Cancer Genome Atlas Program. The results of this research could lead to a translational application of understanding where this orphan NHR fits into the development and progression of cancer. As a quickly growing field, cancer epigenetics is a key player in the ongoing pursuit for identifying biomarkers that may be pertinent in future therapeutic applications.

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          Author and article information

          Journal
          J Endocr Soc
          J Endocr Soc
          jes
          Journal of the Endocrine Society
          Oxford University Press (US )
          2472-1972
          03 May 2021
          03 May 2021
          03 May 2021
          : 5
          : Suppl 1 , ENDO 2021 Abstracts Annual Meeting of the Endocrine Society
          : A506-A507
          Affiliations
          UNIVERSITY OF SAN FRANCISCO , San Francisco, CA, USA
          Article
          bvab048.1035
          10.1210/jendso/bvab048.1035
          8090728
          504fcd33-e7d3-44a3-abfd-6560b07cbe3e
          © The Author(s) 2021. Published by Oxford University Press on behalf of the Endocrine Society.

          This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence ( http://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com

          History
          Page count
          Pages: 2
          Categories
          Genetics and Development (including Gene Regulation)
          From Bench to Bedside: Genetics, Development and Cell Signaling in Endocrinology
          AcademicSubjects/MED00250

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