Distinct patterns of histone modifications at cardiac-specific gene promoters between cardiac stem cells and...

Mesenchymal stem cells (MSCs) and cardiac stem cells (CSCs) possess different potential to develop into cardiomyocytes. The mechanism underlying cardiomyogenic capacity of MSCs and CSCs remains elusive. It is well established that histone modifications correlate with gene expression and contribute to cell fate commitment. Here we hypothesize that specific histone modifications accompany cardiac-specific gene expression, thus determining the differentiation capacity of MSCs and CSCs toward heart cells. Our results indicate that, at the promoter regions of cardiac-specific genes (Myh6, Myl2, Actc1, Tnni3, and Tnnt2), the levels of histone acetylation of H3 (acH3) and H4 (acH4), as a mark indicative of gene activation, were higher in CSCs (Sca-1(+)CD29(+)) than MSCs. Additionally, lower binding levels of histone deacetylase (HDAC) 1 and HDAC2 at promoter regions of cardiac-specific genes were noticed in CSCs than MSCs. Treatment with trichostatin A, an HDAC inhibitor, upregulated cardiac-specific gene expression in MSCs. Suppression of HDAC1 or HDAC2 expression by small interfering RNAs led to increased cardiac gene expression and was accompanied by enhanced acH3 and acH4 levels at gene loci. We conclude that greater levels of histone acetylation at cardiac-specific gene loci in CSCs than MSCs reflect a stronger potential for CSCs to develop into cardiomyocytes. These lineage-differential histone modifications are likely due to less HDAC recruitment at cardiac-specific gene promoters in CSCs than MSCs.