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AKAP12alpha, an atypical serum response factor-dependent target gene
Jeffrey W Streb1, Joseph M Miano
1Center for Cardiovascular Research in the Aab Institute of Biomedical Sciences, University of Rochester School of Medicine, Rochester, New York 14642, USA.
The Journal of Biological Chemistry
|December 14, 2004
Summary
Serum response factor (SRF) controls AKAP12alpha expression via specific promoter elements. Unique flanking sequences dictate gene regulation, revealing atypical SRF-dependent target genes.
Area of Science:
- Molecular Biology
- Gene Regulation
- Transcription Factors
Background:
- AKAP12 gene has three isoforms regulated by distinct promoters.
- Serum response factor (SRF) is a key transcription factor in cellular processes.
- SRF binding sites were identified in the AKAP12alpha promoter.
Purpose of the Study:
- To investigate the role of SRF in AKAP12alpha expression.
- To understand how SRF regulates the AKAP12alpha promoter.
- To identify factors determining the unique regulatory properties of AKAP12alpha.
Main Methods:
- Reporter assays were used to measure promoter activity.
- RNA interference (RNAi) was employed to assess SRF function.
- Analysis of SRF-binding sites (CArG boxes) and flanking sequences was performed.
Main Results:
- SRF is essential for AKAP12alpha expression.
- SRF binds to two CArG boxes in the AKAP12alpha promoter with varying affinities.
- AKAP12alpha expression is not modulated by typical growth or differentiation signals.
- Flanking sequences, particularly the absence of Ets binding sites, confer resistance to growth stimulation.
- Myocardin sensitivity depends on flanking sequences and a consensus CArG box.
Conclusions:
- AKAP12alpha represents a novel class of atypical SRF-dependent genes.
- Flanking sequences play a critical role in modulating SRF-target gene sensitivity to stimuli.
- This study provides new insights into SRF-myocardin interactions and gene regulation.