School of Life Sciences, Ecole Polytechnique Fédérale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Laboratory of Molecular Virology, Institute of Human Genetics, CNRS UPR1142, MGX-Montpellier GenomiX, 141 rue de la Cardonille, 34396 Montpellier, France.
Philos Trans R Soc Lond B Biol Sci. 2020 Mar 30;375(1795):20190334. doi: 10.1098/rstb.2019.0334. Epub 2020 Feb 10.
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 the human K562 erythro-leukaemia cell line. We found that the regulator can associate with a wide range of nucleic acid binding proteins, nucleosome remodellers, chromatin modifiers and other transcription modulators. We further determined that KAP1 is recruited at actively transcribed polymerase II promoters, where its depletion resulted in pleomorphic effects, whether expression of these genes was normally constitutive or inducible, consistent with the breadth of possible KAP1 interactors. This article is part of a discussion meeting issue 'Crossroads between transposons and gene regulation'.
KAP1（KRAB 相关蛋白 1）最为人所知的是作为一种共抑制因子，负责诱导异染色质形成，特别是在转座元件上。然而，也有人观察到它与活跃表达基因的转录起始位点结合。为了解决这个矛盾，我们在人类 K562 红白血病细胞系中对 KAP1 的蛋白质相互作用组进行了表征。我们发现该调节剂可以与广泛的核酸结合蛋白、核小体重塑因子、染色质修饰剂和其他转录调节剂结合。我们进一步确定 KAP1 被招募到活跃转录的聚合酶 II 启动子上，其耗尽导致多态效应，无论这些基因的表达是正常组成型还是诱导型，这与 KAP1 相互作用者的广泛性一致。本文是“转座子与基因调控的交叉点”讨论专题的一部分。
