A Comprehensive Catalog of Human KRAB-associated Zinc Finger Genes: Insights into the Evolutionary History of a Large Family of Transcriptional Repressors
Krueppel-type zinc finger (ZNF) motifs are prevalent components of transcription factor proteins in all eukaryotic species. In mammals, most ZNF proteins comprise a single class of transcriptional repressors in which a chromatin interaction domain, called the Krueppel-associated box (KRAB) is attached to a tandem array of DNA-binding zinc-finger motifs. KRAB-ZNF loci are specific to tetrapod vertebrates, but have expanded dramatically in numbers through repeated rounds of segmental duplication to create a gene family with hundreds of members in mammals. To define the full repertoire of human KRAB-ZNF proteins, we searched the human genome for key motifs and used them to construct and manually curate gene models. The resulting KRAB-ZNF gene catalog includes 326 known genes, 243 of which were structurally corrected by manual annotation, and 97 novel KRAB-ZNF genes; this single family therefore comprises 20% of all predicted human transcription factor genes. Many of the genes are alternatively spliced, yielding a total of 743 distinct predicted proteins. Although many human KRAB-ZNF genes are conserved in mammals, at least 136 and potentially more than 200 genes of this type are primate-specific including many recent segmental duplicates. KRAB-ZNF genes are active in a wide variety of human tissues suggesting roles in many key biological processes, but most member genes remain completely uncharacterized. Because of their sheer numbers, wide-ranging tissue-specific expression patterns, and remarkable evolutionary divergence we predict that KRAB-ZNF transcription factors have played critical roles in crafting many aspects of human biology, including both deeply conserved and primate-specific traits.
- Research Organization:
- Lawrence Livermore National Laboratory (LLNL), Livermore, CA
- Sponsoring Organization:
- USDOE
- DOE Contract Number:
- W-7405-ENG-48
- OSTI ID:
- 885364
- Report Number(s):
- UCRL-JRNL-216004
- Journal Information:
- Genome Research, Journal Name: Genome Research Journal Issue: 5 Vol. 16
- Country of Publication:
- United States
- Language:
- English
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