Cohesin Rad21 Mediates Loss of Heterozygosity and Is Upregulated via Wnt Promoting Transcriptional Dysregulation in Gastrointestinal Tumors Academic Article uri icon

abstract

  • Loss of heterozygosity (LOH) of the adenomatous polyposis coli (APC) gene triggers a series of molecular events leading to intestinal adenomagenesis. Haploinsufficiency of the cohesin Rad21 influences multiple initiating events in colorectal cancer (CRC). We identify Rad21 as a gatekeeper of LOH and a β-catenin target gene and provide evidence that Wnt pathway activation drives RAD21 expression in human CRC. Genome-wide analyses identified Rad21 as a key transcriptional regulator of critical CRC genes and long interspersed element (LINE-1 or L1) retrotransposons. Elevated RAD21 expression tracks with reactivation of L1 expression in human sporadic CRC, implicating cohesin-mediated L1 expression in global genomic instability and gene dysregulation in cancer.

authors

  • Xu, Huiling
  • Yan, Yuqian
  • Deb, Siddhartha
  • Rangasamy, Danny
  • Germann, Markus
  • Malaterre, Jordane
  • Eder, Noreen C
  • Ward, Robyn L
  • Hawkins, Nicholas J
  • Tothill, Richard W
  • Chen, Long
  • Mortensen, Neil J
  • Fox, Stephen B
  • McKay, Michael J
  • Ramsay, Robert G

publication date

  • 2014