Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker

Bongjune Yoon, Kerry Herman, Benjamin Hu, Yoon Jung Park, Anders Lindroth, Adam Bell, Adam G. West, Yanjie Chang, Aimee Stablewski, Jessica C. Piel, Dmitri I. Loukinov, Victor V. Lobanenkov, Paul D. Soloway

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78 Citations (Scopus)

Abstract

Imprinted methylation of the paternal Rasgrf1 allele in mice occurs at a differentially methylated domain (DMD) 30 kbp 5′ of the promoter. A repeated sequence 3′ of the DMD regulates imprinted methylation, which is required for imprinted expression. Here we identify the mechanism by which methylation controls imprinting. The DMD is an enhancer Mocker that binds CTCF in a methylation-sensitive manner. CTCF bound to the unmethylated maternal allele silences expression. CTCF binding to the paternal allele is prevented by repeat-mediated methylation, allowing expression. Optimal in vitro enhancer-blocking activity requires CTCF binding sites. The enhancer blocker can be bypassed in vivo and imprinting abolished by placing an extra enhancer proximal to the promoter. Together, the repeats and the DMD constitute a binary switch that regulates Rasgrf1 imprinting.

Original languageEnglish
Pages (from-to)11184-11190
Number of pages7
JournalMolecular and cellular biology
Volume25
Issue number24
DOIs
Publication statusPublished - 2005 Dec

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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    Yoon, B., Herman, K., Hu, B., Park, Y. J., Lindroth, A., Bell, A., West, A. G., Chang, Y., Stablewski, A., Piel, J. C., Loukinov, D. I., Lobanenkov, V. V., & Soloway, P. D. (2005). Rasgrf1 imprinting is regulated by a CTCF-dependent methylation-sensitive enhancer blocker. Molecular and cellular biology, 25(24), 11184-11190. https://doi.org/10.1128/MCB.25.24.11184-11190.2005