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enter image description here In order for a specific gene to be expressed in the mammal’s cells, all of the gene’s binding sites must be bound by transcriptional activators. The mammal’s skin cells contain activators that bind to sites B, D, and E, while the mammal’s liver cells contain activators that bind to sites A, C, and E. (From Khan academy)

Why can both Gene 2 and Gene 4 be expressed in skin cells? I think Gene 4 can't since it doesn't have site E.

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You understand this wrong: All present enhancers of a gene must be bound by a enhancing factor, not all factors of a certain cell types have to be bound. So when skin cells contain activators for B, D and E they can activate gene 2 and 4 of your example, but not gene 3 since the activators for A and C are missing.

So when you have a gene containing any combination of B, D and E, its activation in skin cells is possible according to this model. The same is true for any combination of A, C and E for liver cells. The special case would be a gene having E as the only enhancer as this could be activated in both, liver and skin cells.

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  • $\begingroup$ This is the right answer, but enhancers tend to act in surprising ways. The question works tautologically if you define expression as the highest level of expression, the binding sites as only those with an observed positive effect on expression, and ignore all other interactions. Otherwise you could be in for surprises. :) $\endgroup$
    – Mike Serfas
    Apr 12, 2021 at 14:56
  • $\begingroup$ @MikeSerfas I know, I worked for quite a while on the regulation of gene expression and enhancers. Sometimes they bind coordinated, sometimes seemingly identical sites are only bound under certain conditions etc. This is a simplified example, for this purpose this should be fine I think. $\endgroup$
    – Chris ♦
    Apr 12, 2021 at 16:35

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