Premium
MPP 8 and SIRT 1 crosstalk in E‐cadherin gene silencing and epithelial–mesenchymal transition
Author(s) -
Sun Lidong,
Kokura Kenji,
Izumi Victoria,
Koomen John M,
Seto Edward,
Chen Jiandong,
Fang Jia
Publication year - 2015
Publication title -
embo reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 4.584
H-Index - 184
eISSN - 1469-3178
pISSN - 1469-221X
DOI - 10.15252/embr.201439792
Subject(s) - gene silencing , epigenetics , acetylation , microbiology and biotechnology , epithelial–mesenchymal transition , biology , methylation , gene knockdown , histone , dna methylation , cancer research , chemistry , gene , gene expression , genetics , transition (genetics)
As a critical developmental process, epithelial–mesenchymal transition ( EMT ) involves complex transcriptional reprogramming and has been closely linked to malignant progression. Although various epigenetic modifications, such as histone deacetylation and H3K9 methylation, have been implicated in this process, how they are coordinated remains elusive. We recently revealed that MPP 8 couples H3K9 methylation and DNA methylation for E‐cadherin gene silencing and promotes tumor cell migration, invasion, and EMT . Here, we show that MPP 8 cooperates with the class III HDAC SIRT 1 in this process through their physical interaction. SIRT 1 antagonizes PCAF ‐catalyzed MPP 8‐K439 acetylation to protect MPP 8 from ubiquitin‐proteasome‐mediated proteolysis. Conversely, MPP 8 recruits SIRT 1 for H4K16 deacetylation after binding to methyl‐H3K9 on target promoters. Consequently, disabling either MPP 8 methyl‐H3K9 binding or SIRT 1 interaction de‐represses E‐cadherin and reduces EMT phenotypes, as does knockdown of MPP 8 or SIRT 1 in prostate cancer cells. These results illustrate how SIRT 1 and MPP 8 reciprocally promote each other's function and coordinate epithelial gene silencing and EMT .