The LIM protein AJUBA recruits protein arginine methyltransferase 5 to mediate SNAIL-dependent transcriptional repression.
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.
Hou
Zhaoyuan
Z
The Wistar Institute, 3601 Spruce Street, Philadelphia, PA 19104, USA.
Peng
Hongzhuang
H
Ayyanathan
Kasirajan
K
Yan
Kai-Ping
KP
Langer
Ellen M
EM
Longmore
Gregory D
GD
Rauscher
Frank J
FJ
D021581:Active Transport, Cell Nucleus; D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D015820:Cadherins / Q000235:genetics / Q000378:metabolism; D002460:Cell Line; D017931:DNA Primers / Q000235:genetics; D018398:Homeodomain Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D060588:LIM Domain Proteins; D051379:Mice; D008954:Models, Biological; D008969:Molecular Sequence Data; D046912:Multiprotein Complexes; D011401:Promoter Regions, Genetic; D011485:Protein Binding; D011496:Protein Methyltransferases / Q000235:genetics* / Q000378:metabolism*; D011484:Protein-Arginine N-Methyltransferases; D034741:RNA, Small Interfering / Q000235:genetics; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*; D014162:Transfection
D015820:Cadherins; D017931:DNA Primers; D018398:Homeodomain Proteins; D060588:LIM Domain Proteins; D046912:Multiprotein Complexes; D034741:RNA, Small Interfering; D011994:Recombinant Proteins; D000071250:Snail Family Transcription Factors; D014157:Transcription Factors; C485607:ajuba protein, mouse; D011496:Protein Methyltransferases; C400529:PRMT5 protein, human; D011484:Protein-Arginine N-Methyltransferases