Lysine- and arginine-specific methyltransferases have been shown to act as either direct or secondary transcriptional co-activator of the estrogen receptor (ERα). However, little is known about the role of protein l-isoaspartyl O-methyltransferase (PIMT) on transcriptional regulation. Here, we show that PIMT acts as a co-activator for ERα-mediated transcription. Activation of the estrogen response element (ERE) promoter by β-estradiol (E2) was suppressed by knockdown of PIMT, and enhanced by overexpression of wild-type PIMT. However, the ERE promoter activity was resistant to E2 stimulation in cells overexpressing a catalytically inactive PIMT mutant, G88A. Consistent with these results, the expression of the endogenous ERα response gene trefoil factor 1 (TFF1) by E2 was completely abrogated by PIMT depletion and decreased to approximately 50% when PIMT mutant G88A was expressed. In addition, over-expression of PIMT significantly increased the levels of TFF1 mRNA in the presence or absence of E2. Interestingly, PIMT interacted with ERα and was distributed to the cytosol and the nucleus. The chromatin immunoprecipitation analysis revealed that PIMT was recruited to the promoter of TFF1 gene together with ERα in an E2-dependent manner, which was accompanied by uploading of RNA polymerase II on the promoter. Taken together, the results suggest that PIMT may act as a co-activator in ERα-mediated transcription through its recruitment to the promoter via interacting with ERα.
|Number of pages||7|
|Journal||Biochemical and Biophysical Research Communications|
|Publication status||Published - 2012 Apr 6|
Bibliographical noteFunding Information:
This research was supported by Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology (2011-0028282, 2011-0028283, 2011-0028284).
All Science Journal Classification (ASJC) codes
- Molecular Biology
- Cell Biology