Requirement of protein l-isoaspartyl O-methyltransferase for transcriptional activation of trefoil factor 1 (TFF1) gene by estrogen receptor alpha

Jong Woo Park, Jae Cheol Lee, Shin Won Ha, So Young Bang, Eun Kyung Park, Sang Ah Yi, Min Gyu Lee, Dae Sung Kim, Ki Hong Nam, Ji Hee Yoo, So Hee Kwon, Jeung Whan Han

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6 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)223-229
Number of pages7
JournalBiochemical and Biophysical Research Communications
Volume420
Issue number2
DOIs
Publication statusPublished - 2012 Apr 6

All Science Journal Classification (ASJC) codes

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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