![]() |
Figure 7: A model for chromatin dynamics in Oct-4 associated hESC pluripotency maintenance and differentiation. The genomic plasticity of the undifferentiated state of hESCs (hESC Colony Zone 1) is enabled by a highly dynamic globally active (open) chromatin which reflects a balance between acetylation and deacetylation. Oct-4 maintains this equilibrium and hence a pluripotent genome by recruiting active chromatin-remodeling-complexes containing HDAC1, Brg-1, and hSNF2H. The loss of this balance, as a result of decreasing in either Oct-4 or HDAC1, induces hyperacetylation and subsequent onset of differentiation in cells at transitional Zone 2. Differentiation is stabilized in cells that have migrated into Zone 3, as an Oct-4 independent deacetylation process promotes the compaction of hypoacetylated nucleosomes into a general repressive (closed) chromatin structure. The stylized graph below this model schematizes the equilibriums between acetylation (Ac) and deacetylation (Dac) as differentiation progresses -- from acetylated to transiently hyperacetylated to hypoacetylated. |