Abstract
dc:description.abstract<p>DAX-1 (NR0B1) is an orphan nuclear receptor that plays a key role in the development and maintenance of steroidogenic tissue in mammals. Dax-1 is also expressed in mouse embryonic stem (ES) cells and is required to maintain pluripotency. Duplication of the X-chromosome in the region containing the NR0B1 gene results in sex reversal, and mutations in NR0B1 cause adrenal hypoplasia congenita. DAX-1 has been observed to act as a corepressor of other nuclear receptors including androgen receptor (AR), estrogen receptor (ER), and steroidogenic factor 1 (SF-1). In addition to pluripotent ES cells, DAX-1 is primarily expressed in select tissues of the body such as testes, ovaries, adrenal cortex and breast. In some cases, changes in DAX-1 expression may serve as an indicator of aberrant growth. For example, DAX-1 expression is greatly reduced in ER+ breast cancer patient samples and several ER+ cell lines; however the mechanism leading to this change in DAX-1 expression is unknown. Here, we propose that expression of DAX-1 may be governed by epigenetic mechanisms. </p> <p>We sought to determine whether promoter region CpG island methylation and expression of DAX-1 were inversely related , and if the loss of DAX-1 expression in the breast cancer cell line MCF-7 is due to epigenetic mechanisms. Using gene expression assays and bisulfite sequencing, we have confirmed the relationship between methylation status and DAX-1 expression in MCF7 and A549 cancer cell lines. We have further analyzed the DAX-1 CpG island to observe the presence of epigenetic readers MeCP2 and MBD1 that link methylation to gene repression, suggesting DAX-1 is expressed and regulated differentially by epigenetic mechanisms in the cancer cell lines MCF7 and A549.</p>
Degree
thesis:*- Name thesis:degree_name
- Master of Science in Biology
- Level thesis:degree_level
- Thesis
- Discipline thesis:degree_discipline
- Biology
- Year dc:date.available
- 2014
Author and committee
dc:creator, dc:contributor.*- Author dc:creator
-
- Heskett, Michael B
- Contributors dc:contributor
-
- Christina Tzagarakis-Foster
- James Sikes
- Juliet Spencer
Subjects
dc:subject × 10Identifiers
dc:identifier.*- Repository record dc:identifier
- https://repository.usfca.edu/thes/116
- OAI identifier oai:identifier
- oai:repository.usfca.edu:thes-1132