All in the Family: the BTB/POZ, KRAB, and SCAN Domains

Understanding the mechanisms by which specific genes are expressed in a temporal or tissue-specific manner is a central problem in biology.Transcription factors play a key role in this process.These proteins are modular and can be classified based on the structure of the domain that binds DNA.One type of DNA binding domain is defined by its requirement for zinc and has been designated a zinc finger motif (reviewed in reference 28).In this group, the C 2 H 2 zinc fingers represent one of the most common types of DNA binding domains.The motif frequently occurs in tandem repeats and is defined by two cysteine and two histidine residues that coordinate a zinc ion and fold the domain into a finger-like projection that can interact with DNA (28).There are approximately 600 to 700 genes in the human genome encoding C 2 H 2 motifs (7, 48a), suggesting that this class of transcription factors represents a substantial portion of the genes in the human genome.Accompanying the zinc finger elements in the C 2 H 2 class of zinc finger transcription factors are a variety of extended sequence motifs.These structural modules regulate subcellular localization, DNA binding, and gene expression by controlling selective association of the transcription factors with each other or with other cellular components.In the C 2 H 2 class of zinc fingers, these associated modules include the poxvirus and zinc finger (POZ) domain ( 5), which is also known as the BTB domain (Broad-Complex, Tramtrack, and Bric-a-brac), the Kruppel-associated box (KRAB) (7), and the newly defined SCAN domain (51).These domains define subgroups and may provide insights into the functions of the members of this large family of zinc finger transcription factors.Here each of these domains will be introduced and representative members of the BTB/POZ and KRAB domain families will be used to place the more recently described SCAN domain family of transcription factors in perspective.