Kap1

Kap1, short for KRAB-associated protein 1, is a transcriptional corepressor that serves as a central scaffold for silencing chromatin. It is recruited to chromatin by KRAB-containing zinc finger proteins (KZFPs), which recognize specific DNA sequences and guide Kap1 to those sites to initiate repression. This mechanism is especially important for silencing transposable elements and regulating nearby genes.

Kap1 belongs to the TRIM protein family and contains an N-terminal RBCC motif (RING finger, B-boxes, and coiled-coil domain) that facilitates protein–protein interactions. Its C-terminal region interfaces with chromatin modifiers, most notably the histone methyltransferase SETDB1, which deposits H3K9me3 marks that recruit heterochromatin protein 1 (HP1). Kap1 also interacts with DNA methylation pathways, helping to maintain DNA methylation patterns in cooperation with DNMTs. Through these interactions, Kap1 promotes the establishment and maintenance of a repressive chromatin state.

Functionally, Kap1 regulates gene expression programs during development and cellular differentiation, contributes to genome stability by repressing repetitive elements, and participates in imprinting and X-chromosome inactivation in some contexts. In embryonic development, loss or dysfunction of Kap1 can lead to derepression of endogenous retroelements and severe developmental defects in model organisms, underscoring its essential role.

Kap1 is widely studied for its role as a universal transcriptional corepressor that enables KRAB zinc finger proteins to shape the epigenome and transcriptional landscape across various cell types and developmental stages.