KAP-1 Corepressor Protein Interacts and Colocalizes with Heterochromatic and Euchromatic HP1 Proteins: a Potential Role for Krüppel-Associated Box–Zinc Finger Proteins in Heterochromatin-Mediated Gene Silencing

• DOI: 10.1128/mcb.19.6.4366
• Publication Date: 2015-10-26T10:18:57Z
• Authors: Robert F. Ryan; David C. Schultz; Kasirajan Ayyanathan; Prim B. Singh; Josh R. Friedman; William J. Freder...; Frank J. Rauscher
• Keywords: Heterochromatin protein 1; Corepressor; Krüppel; Euchromatin; Chromodomain

Krüppel-associated box (KRAB) domains are present in approximately one-third of all human zinc finger proteins (ZFPs) and potent transcriptional repression modules. We have previously cloned a corepressor for the KRAB domain, KAP-1, which is required KRAB-mediated vivo. To characterize mechanism utilized by we analyzed ability KAP-1 to interact with murine (M31 M32) (HP1alpha HP1gamma) homologues HP1 protein family, class nonhistone heterochromatin-associated well-established epigenetic gene silencing function Drosophila. In vitro studies confirmed that capable directly interacting M31 hHP1alpha, normally found centromeric heterochromatin, as well M32 hHP1gamma, both euchromatin. Mapping region interaction showed amino acid substitutions abolish binding reduce mediated observed colocalization interphase nuclei, lending support biochemical evidence KAP-1. The sometimes subnuclear territories potential pericentromeric whereas occurs punctate euchromatic throughout nucleus. This work suggests recruitment HP1-like products KRAB-ZFP-KAP-1 complex specific loci within genome through formation heterochromatin-like complexes silence activity. speculate gene-specific may be consequence such complexes, ultimately leading silenced genes newly formed heterochromatic chromosomal environments.