ChIP-exo and ChIP-seq of human KRAB-ZNFs transduced in HEK 293T cells
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ABSTRACT: Kruppel-associated box (KRAB)-containing zinc-finger proteins (KZFPs) represent the largest family of transcription factors encoded by higher vertebrates. Together with their heterochromatin-inducing cofactor KAP1, many act as repressors of endogenous retroelements (EREs) during early embryonic genome reprogramming, yet their widespread expression in adult tissues and enrichment at other genetic loci indicate additional roles. By characterizing the protein interactome of 101 of the ~350 human KZFPs, we uncovered that it is highly diversified for a subset of those. Most of placental mammal- or primate-restricted KZFPs, which primarily bind EREs and constitute 90% of human KZFPs, essentially recruit KAP1 and effectors. However, certain KZFPs conserved in placental mammals and more distant clades associated with factors related to functions such as genome architecture or RNA processing. Additionally, members of the most conserved human KZFPs did not appear to interact with KAP1. Nevertheless, KZFPs from coelacanth, our most distant KZFP-encoding relative, bind KAP1 from this species. We thus propose that KZFPs first emerged as ERE-controlling repressors, had their pool continuously renewed by turn-over of their hosts’ ERE loads, thereby yielded largely species-specific sets of transcriptional controllers, yet occasionally produced derivatives that escaped this evolutionary flushing by development of novel functions and exaptation.
ORGANISM(S): Homo sapiens
PROVIDER: GSE120539 | GEO | 2019/08/12
REPOSITORIES: GEO
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