The aging myocardium expresses many gene transcripts that are normally expressed during embryonic and fetal development. Using transcriptome-based and promoter-based techniques, we have worked towards understanding the mechanisms underlying this control of gene expression both in models of development and in aging. Serial analysis of gene expression (SAGE) yields a quantitative, representative and comprehensive differential gene expression profile. We have employed SAGE analysis to generate a quantitative transcript assessment that has proven to be much more rapid and economical than other techniques. We used an RT-PCR based technique to determine the time points where a number of mesodermal and cardiac-restricted gene products are expressed in in vitro differentiated EC derived cardiomyocytes, and more recently feeder layers general employed to maintain embryonic stem cells. These latter studies were designed to identify factors that could possibly reprogram cells to become more multipotent.? We have utilized quantitative PCR and in situ hybridizations to analyze the temporal and spatial distribution of a number of the most differentially regulated transcripts identified by SAGE, several of which have shown a cardiac predominance in either fetal or adult heart. The novel gene products identified in this study provide a framework for the analysis of pre- and early cardiac developmental processes in human and mouse embryonic stem cells and are the subject of active investigation. Included among these gene transcripts that have been subjected to follow-up analysis are Cripto and pleiotrophin.? Two promoter regions that control the expression of genes important to cardiac function (Na/Ca exchanger and the sarco(endo)plasmic reticulum Ca ATPase, SERC) have also been analysed. We have shown that an upstream portion of the multipartitite Na/Ca exchanger promoter is regulated at least in part by GATA-4 and GATA-6 transcription factors, which may control, at least in part, the expression of the Na/Ca exchanger both during development and with aging. Recently we also demonstrated the critical role of SP1 factors in the regulation of the human SERCA2 gene promoter in neonatal rat cardiomyocytes. The control of this promoter depends on the binding of these factors to specific cis-elements located in the promimal promoter.
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