KRAB Zinc Finger Proteins: A Family of Repressors Mediating Heterochromatin-Associated Gene Silencing

Abstract

Krüppel-associated box (KRAB) domain, present at the N terminus of mammalian C2H2 zinc finger proteins, binds KAP-1 (also named TIF1$β$ or KRIP-1) that binds HP1$α$ and SETDB1 (H3-K9 methyltransferase) as well as NuRD complexes (histone deacetylases). The KRAB domain tethers these binding proteins to a specific gene recognized by zinc fingers, resulting in a heterochromatin-associated, strong, long-term repression of the gene. The importance of such repression is reflected in the large number (two hundred ninety) of the KRAB zinc finger protein genes in the human genome and revealed by early stage-development failure of mouse embryos lacking the common corepressor, KAP-1 (TIF1$β$). Many reports have described KRAB zinc finger proteins that participate in a variety of cellular processes including development of organs and cell types such as heart, bone, sperm and hematopoietic cells. Some KRAB zinc finger proteins have an additional repression mechanism that is KRAB domain-independent and involves histone deactylases or NSD1 histone lysine methyltrasferase.