GSE106975
KAP1 targets actively transcribed genomic loci to exert pleomorphic effects on RNA Polymerase II- and III-mediated expression [RNA-Seq, small RNA-Seq]
KAP1 (KRAB-associated protein 1) is best known as a co-repressor responsible for inducing heterochromatin formation notably at transposable elements. However, it has also been observed to bind the transcription start site of actively expressed genes. To address this paradox, we characterized the protein interactome of KAP1 in human embryonic stem cells and in the K562 erythro-leukemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodelers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited not only at actively transcribed polymerase II promoters, but also at genetic units driven by polymerase III, for instance tRNA genes. While KAP1 depletion induced a mild downregulation of these genes, at PolII-transcribed units it resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors Overall design: RNA-sequencing analysis of Hepa 1.6 WT and Kap1 knock-down cells. Small RNA-sequencing analysis of Hepa 1.6 WT and Kap1 knock-down cells, and of primary murine hepatocytes WT and Kap1 knock-out.