Derangement of a Factor Upstream of RARα Triggers the Repression of a Pleiotropic Epigenetic Network
2009

How CRABP2 Affects Gene Regulation in Cancer

publication Evidence: high

Author Information

Author(s): Francesca Corlazzoli, Stefano Rossetti, Gaia Bistulfi, Ren Mingqiang, Nicoletta Sacchi

Primary Institution: Cancer Genetics Program, Roswell Park Cancer Institute, Buffalo, New York, United States of America

Hypothesis

Inheritable aberrant chromatin states in cancer and aging are caused by genetic/environmental factors.

Conclusion

Interference with CRABP2 function induces epigenetic repression of a RA-regulated gene network downstream of RARα, leading to significant biological outcomes.

Supporting Evidence

  • CRABP2 is critical for transporting retinoic acid to RARα.
  • Knockdown of CRABP2 leads to transcriptional repression of RA-responsive genes.
  • The chromatin state becomes unresponsive to retinoic acid after CRABP2 interference.
  • Hypermethylation of RARβ2 and CRBP1 correlates with their silencing.
  • Impaired CRABP2 function results in loss of acinar morphogenesis in breast epithelial cells.

Takeaway

When a protein called CRABP2 doesn't work right, it can cause important genes to be turned off in a way that can be passed down to future cells.

Methodology

The study involved targeting CRABP2 in human mammary epithelial cells to observe effects on gene expression and chromatin state.

Participant Demographics

Human mammary epithelial cells were used in the study.

Statistical Information

P-Value

p<0.05

Statistical Significance

p<0.05

Digital Object Identifier (DOI)

10.1371/journal.pone.0004305

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