The largest family of zinc-finger transcription factors comprises those containing the Krüppel-associated box (or KRAB domain), which are present only in tetrapod vertebrates. Many genes encoding KRAB-containing proteins are arranged in clusters in the human genome, with one cluster close to chromosome 9ql3 and others in centromeric and telomeric regions of other chromosomes, but other genes occur individually throughout the genome. The KRAB domain, which is found in the amino-terminal region of the proteins, behaves as a transcriptional repressor domain by binding to corepressor proteins, whereas the C2H2 zinc-finger motifs bind DNA. The functions currently proposed for members of the KRAB-containing protein family include transcriptional repression of RNA polymerase I, II, and III promoters and binding and splicing of RNA. Members of the family are involved in maintenance of the nucleolus, cell differentiation, cell proliferation, apoptosis, and neoplastic transformation.