3-D packaging of DNA regulates cell identity

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 right 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. Credit: Artwork by Kate Isenberg kateisenberg.com

The fundamental mechanisms governing how cells form an identity such as becoming a muscle cell or a nerve cell are not fully understood. Multiple diseases, including cancer, have been linked to cells going down the wrong developmental path during maturation. A new study from the Perelman School of Medicine at the University of Pennsylvania suggests that the ability of a stem cell to differentiate into cardiac muscle (and by extension other cell types) depends on what portions of the genome are available for activation, which is controlled by the location of DNA in a cell’s nucleus.


“The basis of this study is understanding the ability of a cell to respond to molecular cues to correctly become one cell type or another,” said senior author, Rajan Jain, MD, an assistant professor of…

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