Key result
Mef2c is the most critical cis-acting element in the CARK promoter, and CARK transcription can be down-regulated by MEF2C antisense in mouse heart tissue.
This preclinical study identifies Mef2c as an essential regulatory element required for the unique expression of the cardiac-specific CARK gene.
Does not support clinical translation; leaves open Mef2c-CARK regulation as hypothesis-generating for human cardiac studies.
The cardiac ankyrin repeat kinase (CARK) gene, also named TNNI3K for its interaction with cardiac troponin I, is both a unique expression and heart-enriched gene. To understand the mechanisms of CARK gene expression and regulation, we first cloned the full-length mRNA sequence and mapped the transcription start site of the mouse CARK gene and characterized its promoter regions. Two transcriptional isoforms of the CARK gene were identified in mouse heart tissue. Truncation analysis of the CARK promoter identified a minimal 151 bp region that has strong basal transcription activity. Mutational analysis revealed five conserved cis-acting elements in this 151-bp long minimal promoter. Mutational and loss-of-functional analysis and co-transfection studies indicated that MEF2 binding region is the most critical cis-acting element in the CARK promoter, and CARK transcription level can be down-regulated by MEF2C antisense. Binding to the MEF2 sites by Mef2c protein was confirmed by electrophoretic mobility shift assay and competition and supershift electrophoretic mobility shift assays.
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Wang et al. (2007) studied CARK gene expression. MEF2C antisense was evaluated on CARK gene expression and regulation mechanisms. Mef2c is the most critical cis-acting element in the CARK promoter, and CARK transcription can be down-regulated by MEF2C antisense in mouse heart tissue.
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