Figure 3.

The silent sister hypothesis. Prior to replication (top panel) the DNA in a chromosome has two complementary strands: “Crick” (5′ to 3′, top strand, blue line) and “Watson” (3′ to 5′, bottom strand, red line). A single gene “A” is shown which is expressed as a result of specific chromatin marks (+ sign in figure). Following DNA replication (middle panels) “Watson” and Crick“ DNA template strands are copied to yield two sister chromatids with identical DNA sequence. The silent sister hypothesis proposes that not all chromatin marks are copied onto both sister chromatids during or following DNA replication. As a result only one sister chromatid will inherit the active chromatin mark (+) and the other sister chromatid (the “silent sister”) will not (−). In the figure active chromatin marks (+) follow the “Watson” DNA template strand and the sister chromatid with the original “Crick” DNA template strand does not have this chromatin mark and therefore does not support expression of gene A (indicated by a small a). Following random segregation of sister chromatids (bottom left panel), the two daughter cells will show “stochastic” variation in the expression of gene A (A or a) which is predicted to follow the parental DNA template strand that was inherited. Note that failure to copy suppressive chromatin marks will result in similar “stochastic” variation in gene expression. If sister chromatids of specific chromosomes are furthermore specifically retained in one of the daughter cells (e.g. via specific chromatin marks at sister chromatid centromeres connecting microtubules to “mother” centrosomes [22], sister chromatid asymmetry in chromatin marks at specific genes could directly regulate gene expression and cell fate as shown (bottom right panel).