Kruppel-like factors

In molecular genetics, the Krüppel-like family of transcription factors (KLFs) are a set of zinc finger DNA-binding proteins that regulate gene expression.

The following human genes encode Kruppel-like factors: KLF1, KLF2, KLF3, KLF4, KLF5, KLF6, KLF7, KLF8, KLF9, KLF10, KLF11, KLF12, KLF13, KLF14, KLF15, KLF16, KLF17

Each family member has a characteristic set of three zinc fingers at its C-terminus. These fingers are related to those of the archetypal Drosophila melanogaster regulatory protein Krüppel. Hence the family is named after Krüppel and family members are numbered roughly in the order in which they were discovered.

In mammals, there are 17 genes in the KLF family. There are also nine related proteins that form the SP1 subfamily. The transcription factors SP1 to SP9 are similar to the KLFs, but their zinc fingers are closer to the middle of the protein rather than at the C-terminus.

The family is important since it nicely illustrates general features found in transcription factor families and gene families generally.

Firstly, these transcription factors have a simple and well understood structure. Their characteristic zinc finger DNA-binding domain at the C-terminus contains 3 zinc fingers, that each essentially recognize 3 base pairs in DNA. Thus the DNA-binding site recognized by these proteins is of the general form NCR CRC CCN (where N is any base and R is a purine). The functional domains of the KLFs are at the other end of the protein, the N-terminus, and vary between family members. Thus some KLFs activate and others repress gene expression. Some do both. In several cases the mechanisms by which the functional N-terminal domains operate is understood. In the case of KLF3, for example, there is a short motif in the N-terminus (of the form Proline-Isoleucine-Aspartate-Leucine-Serine or PIDLS) that recruits the co-repressor proteins C-terminal Binding Protein 1 and 2 (CTBP1 and CTBP2). CtBP in turn recruits histone modifying enzymes. It brings in histone deacetylases, histone demethylases and histone methylases, which are thought to remove active chromatin marks and lay down repressive marks to eliminate gene expression.

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