MERVL ERVs are derepressed upon KAP1 but not SETDB1 depletion, while MMERVK10C and IAP ERVs are upregulated following depletion of both. (A) Repbase annotations of the LTR and internal regions of full-length MERVL, IAPEz and MMERVK10C elements are shown. Black bars indicate qPCR amplicons for LTRs of each family of element and the internal pol gene region for MERVL. (B) Deregulation of transposable element families in KAP1 and SETDB1 KO mESCs. RNA-seq data for SETDB1  and KAP1  KO lines and the corresponding wt cell lines were used to calculate Z-score values for all annotated retroelements and plotted as shown. (C) KAP1 and SETDB1 were depleted by RNAi in wt TT2 mESCs, and reactivation of MERVL and MMERVK10C elements was determined by qRT-PCR. Mean expression (+/-SD) of each ERV (normalized to β-actin) relative to a scrambled siRNA pool (Scram) is shown for three technical replicates. (D) MERVL is among a small group of transposable elements bound by KAP1 but not SETDB1. RPKM (*10) values generated from published ChIP-seq data for KAP1  and SETDB1  were plotted for all retroelements. Numerous class I and class II ERVs, including IAP subfamilies are enriched for both proteins, which are generally strongly correlated. MERVL elements are modestly enriched for KAP1, but show relatively low levels of SETDB1 coverage. ChIP-seq, chromatin immunoprecipitation sequencing; RPKM, reads per kilobase per million mapped reads.