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SKOV3 cells containing a truncated ARID1a protein have a restricted genome-wide response to glucocorticoids

Research output: Contribution to journalArticle

Original languageEnglish
Pages (from-to)226-235
Number of pages10
JournalMolecular and Cellular Endocrinology
Volume461
Early online date21 Sep 2017
DOIs
DateAccepted/In press - 13 Sep 2017
DateE-pub ahead of print - 21 Sep 2017
DatePublished (current) - 5 Feb 2018

Abstract

AT-rich interacting domain subunit 1a (ARID1a) is an essential SWI/SNF component frequently mutated in human cancers. ARID1a mutations have also been associated with glucocorticoid resistance, potentially related to the well-established role of the SWI/SNF complex in glucocorticoid target gene regulation. Glucocorticoids are steroid hormones important for regulating many physiological processes through the activation of the glucocorticoid receptor (GR). As GR interacts directly with ARID1a, we hypothesized that a truncating ARID mutation would interfere with GR-dependent gene regulation. Using high throughput RNA sequencing (RNA-SEQ) we show a restricted glucocorticoid response in SKOV3 cells, which contain an inactivating ARID1a mutation. We also show a lack of GR binding at the GR-dependent regulatory site in the Period 1 gene, which has previously been shown to require chromatin remodelling. Taken together, our data suggests that ARID1a may be required for regulation of a subset of glucocorticoid responsive genes. In the case of SKOV3 cells, in which ARID1a is mutated, glucocorticoid-dependent transcriptional regulation of these genes is significantly impaired.

    Research areas

  • ARID1a, Glucocorticoid receptor, Glucocorticoids, SWI/SNF, Transcription

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  • Full-text PDF (accepted author manuscript)

    Rights statement: This is the accepted author manuscript (AAM). The final published version (version of record) is available online via Elsevier at https://doi.org/10.1016/j.mce.2017.09.018 . Please refer to any applicable terms of use of the publisher.

    Accepted author manuscript, 2.09 MB, PDF document

    Licence: CC BY-NC-ND

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