Artwork by Kate Isenberg (www.kateisenberg.com).
Cell fate determination requires the coordinated regulation of gene programs involved in development and the maturation of tissues. The team found that Hdac3 influences cell fate determination through its role as a tether that coordinates the three-dimensional organization of chromatin in the nucleus. The illustration (left) represents the interior of the nucleus where individual cell fate is determined by which gene programs are available, while others are stored away in an inaccessible molecular closet. The left image is a 3D representation of the location of the Titin gene (red) in a cardiac myocyte. The nuclear lamina is shown in green and troponin fibers in yellow. Chromatin containing key genes required for particular cell fates are sequestered at the nuclear periphery. Genomic regions containing cardiac genes are released from the nuclear periphery upon differentiation of stem cells into cardiac myocytes.