The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression

Zhaoyuan Hou, Hongzhuang Peng, Kasirajan Ayyanathan, Kai Ping Yan, Ellen M. Langer, Gregory D. Longmore, Frank J. Rauscher

Research output: Contribution to journalArticlepeer-review

152 Scopus citations

Abstract

The SNAIL transcription factor contains C-terminal tandem zinc finger motifs and an N-terminal SNAG repression domain. The members of the SNAIL family have recently emerged as major contributors to the processes of development and metastasis via the regulation of epithelial-mesenchymal transition events during embryonic development and tumor progression. However, the mechanisms by which SNAIL represses gene expression are largely undefined. Previously we demonstrated that the AJUBA family of LIM proteins function as corepressors for SNAIL and, as such, may serve as a platform for the assembly of chromatin-modifying factors. Here, we describe the identification of the protein arginine methyltransferase 5 (PRMT5) as an effector recruited to SNAIL through an interaction with AJUBA that functions to repress the SNAIL target gene, E-cadherin. PRMT5 binds to the non-LIM region of AJUBA and is translocated into the nucleus in a SNAIL-and AJUBA-dependent manner. The depletion of PRMT5 in p19 cells stimulates E-cadherin expression, and the SNAIL, AJUBA, and PRMT5 ternary complex can be found at the proximal promoter region of the E-cadherin gene, concomitant with increased arginine methylation of histones at the locus. Together, these data suggest that PRMT5 is an effector of SNAIL-dependent gene repression.

Original languageEnglish (US)
Pages (from-to)3198-3207
Number of pages10
JournalMolecular and cellular biology
Volume28
Issue number10
DOIs
StatePublished - May 2008
Externally publishedYes

ASJC Scopus subject areas

  • Molecular Biology
  • Cell Biology

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