Chromatin Remodeling and Cardiac Differentiation of Stem Cells

Cell fate commitment is achieved by cell type-specific transcription, which in turn is guided by epigenetic mechanisms. Epigenetic and chromatin modifications play important roles in embryonic development, allowing cells to differentiate into particular lineages. Chromatin remodeling correlates well with gene expression, thus contributes to cell fate commitment. Chromatin remodeling enzymes exist as large complexes and possess one or more types of remodeling activities. These enzymes are divided into two categories. The first one consists of enzymes that posttranslationally modify amino termini of histone proteins, by adding or removing methyl, acetyl, sumo, phosphate, or ubiquitin moieties. The other category uses ATP hydrolysis to disrupt interactions between DNA and histone proteins, leading to changes in nucleosome positioning and higher-order chromatin structure. These enzymes increase DNA accessibility, thus allowing gene regulators or transcription factors to bind in order to modulate gene expression. Cardiac tissue development and differentiation is a complex process that relies on extensive networks of interacting transcription factors. The chromatin remodeling enzymes are closely associated with these networks, thus providing an added layer of complexity and refinement to the regulation of heart development. Brahma related gene-1 (BRG-1) and BRG-1 related factors (BAF-60c, BAF-180, and BAF250a) are some of the chromatin remodeling enzymes that have been implicated in the process of chromatin remodeling and involved in cardiac differentiation. The role of these complexes and other factors in the cardiac differentiation of stem cells will be discussed in this chapter.