Figure 6.

Model for the evolutionally dynamic control of L1. (A) Very ancient L1s (shown in the top row) may have been once recognized by the KRAB/KAP1 system but have since then accumulated mutations (red crosses) abrogating binding by cognate KRAB-ZFPs but also transcription ability. (B) More recent subfamilies recruit KAP1 through sequence-specific KRAB-ZFPs but also may have some mutations taming their baseline expression. (C) The youngest L1 elements are highly transcribed and are not yet recognized by any KRAB-ZFP but produce small RNAs such as piRNAs, which in turn down-regulate their expression via DNA methylation and see their retrotransposition further blocked by proteins such as APOBEC family members.