Abstract 18239: Yy1 Expression is Sufficient for the Mantenance of Cardiac Progenitor Cell State

BACKGROUND: Transcription factors and epigenetic modifiers regulate gene expression during cardiac development. We have previously shown that YY1 is essential for the commitment of mesodermal precursors into cardiac progenitor cells (CPCs); however, the role of YY1 in the maintenance of CPC phenotype and their differentiation into cardiomyocytes is unknown. METHODS AND RESULTS: We performed genome-wide expression analysis and targeted real-time qPCR as well as chromatin immunoprecipitation assays for histone modification in mouse embryonic stem cell (ESC)-derived CPCs with and without YY1 over-expression. We found, by genome-wide transcriptional profiling and phenotypic assays, that YY1 overexpression prevents cardiomyogenic differentiation and maintains the proliferative capacity of CPCs. We show further that the ability of YY1 to regulate CPC phenotype is associated with its ability to modulate histone modifications specifically at a developmentally critical enhancer of Nkx2-5 and other key cardiac tran...