Alterations in chromatin accessibility and DNA methylation in clear cell renal cell carcinoma

M. J. Buck, L. M. Raaijmakers, S. Ramakrishnan, D. Wang, S. Valiyaparambil, S. Liu, N. J. Nowak, R. Pili

Research output: Contribution to journalArticle

Abstract

Recent studies have demonstrated that in clear cell renal cell carcinoma (ccRCC) several chromatin remodeling enzymes are genetically inactivated. Although, growing evidence in cancer models has demonstrated the importance of epigenetic changes, currently only changes in DNA methylation can be accurately determined from clinical samples. To address this limitation, we have applied formaldehyde-assisted isolation of regulatory elements (FAIREs) combined with next-generation sequencing (FAIRE-seq) to identify specific changes in chromatin accessibility in clinical samples of ccRCC. We modified the FAIRE procedure to allow us to examine chromatin accessibility for small samples of solid tumors. Our FAIRE results were compared with DNA-methylation analysis and show how chromatin accessibility decreases at many sites where DNA-methylation remains unchanged. In addition, our FAIRE-seq analysis allowed us to identify regulatory elements associated with both normal and tumor tissue. We have identified decreases in chromatin accessibility at key ccRCC-linked genes, including PBRM1, SETD2 and MLL2. Overall, our results demonstrate the power of examining multiple aspects of the epigenome.

Original languageEnglish (US)
Pages (from-to)4961-4965
Number of pages5
JournalOncogene
Volume33
Issue number41
DOIs
StatePublished - Oct 9 2014
Externally publishedYes

Keywords

  • Epigenetics
  • epigenome
  • FAIRE
  • FAIRE-seq
  • renal cell carcinoma

ASJC Scopus subject areas

  • Molecular Biology
  • Cancer Research
  • Genetics
  • Medicine(all)

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  • Cite this

    Buck, M. J., Raaijmakers, L. M., Ramakrishnan, S., Wang, D., Valiyaparambil, S., Liu, S., Nowak, N. J., & Pili, R. (2014). Alterations in chromatin accessibility and DNA methylation in clear cell renal cell carcinoma. Oncogene, 33(41), 4961-4965. https://doi.org/10.1038/onc.2013.455