PTIP Interacts with MEF2 in Murine Cardiomyocytes under Environmental Stress: A Link between the Epigenome and the Environment
Dandar, Rachel A.
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The ubiquitously expressed nuclear protein Pax transcription activation domain interacting protein, or PTIP, is a part of a histone H3K4 Methyltransferase (HMT) complex that imparts trimethylation groups associated with gene upregulation. Patel et al. (2007) demonstrated that PTIP interacts with the Pax2 family of transcription factors to localize the histone methylation machinery that impart H3K4me3 on DNA regions in human embryonic kidney (HEK293) cells. However, the family of Pax2 transcription factors is not expressed in the heart. In this study, we attempted to identify the specific transcription factor that localizes PTIP to DNA in heart tissue. Preliminary data from Far Western Blot suggested that PTIP interacts with the Myocyte Enhancer Factor 2 (MEF2) family of transcription factors in adult murine cardiomyocytes. In this study, I worked to demonstrate an interaction between PTIP and MEF2 family of transcription factors through both in vitro and in vivo applications of co-immunoprecipitation (Co-IP). When Co-IP was performed on nuclear extract from naïve and osmotically stressed HEK293 cells, PTIP did not interact with MEF2. Similarly, PTIP did not interact with MEF2 when Co-IP was performed on nuclear extract of differentiating C2C12 myocytes, When Co-IP was performed on nuclear extract from naïve adult murine cardiomyocytes, PTIP did not interact with MEF2 or MEF2D; however, when Co-IP was performed on nuclear extract from mechanically stressed adult murine cardiomyocytes, PTIP did interact with MEF2. Thus, PTIP does not interact with MEF2 under normal conditions in adult murine cardiomyocytes, but PTIP does interact with MEF2 when cardiomyocytes have been exposed to environmental stress. In demonstrating this interaction between PTIP and MEF2, we begin to establish a link between environmental signals and epigenetic mechanisms that induce transcriptional changes in mediation of cardiac stress responses.