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Co-option of an existing enhancer in a novel biological context via oCGI gain. In an ancestral species, the enhancer is active in the developing limb and inactive in the developing brain, where the chromatin at the locus is closed. After oCGI gain, CpG-related mechanisms generate open chromatin in the developing brain, which allows existing unconstrained brain TFBSs to be bound. Over time, these and additional TFBSs may gain biological functions and be maintained by selection. The locus becomes a functional enhancer in the developing brain

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