Abstract
Krüppel-like factors (KLF) and specificity proteins (SP) constitute a family of zinc-finger-containing transcription factors that play important roles in a wide range of processes including differentiation and development of various tissues. The human genome possesses 17 KLF genes (KLF1–KLF17) and nine SP genes (SP1–SP9) with diverse functions. We used sequence similarity searches and gene synteny analysis to identify a new putative KLF gene/pseudogene named KLF18 that is present in most of the placental mammals with sequenced genomes. KLF18 is a chromosomal neighbor of the KLF17 gene and is likely a product of its duplication. Phylogenetic analyses revealed that mammalian predicted KLF18 proteins and KLF17 proteins experienced elevated rates of evolution and are grouped with KLF1/KLF2/KLF4 and non-mammalian KLF17. Predicted KLF18 proteins maintain conserved features in the zinc fingers of the SP/KLF family, while possessing repeats of a unique sequence motif in their N-terminal regions. No expression data have been reported for KLF18, suggesting that it either has highly restricted expression patterns and specialized functions, or could have become a pseudogene in extant placental mammals. Besides KLF18 genes/pseudogenes, we identified several KLF18-like genes such as Zfp352, Zfp352-like, and Zfp353 in the genomes of mouse and rat. These KLF18-like genes do not possess introns inside their coding regions, and gene expression data indicate that some of them may function in early embryonic development. They represent further expansions of KLF members in the murine lineage, most likely resulted from several events of retrotransposition and local gene duplication starting from an ancient spliced mRNA of KLF18.
Highlights
Krüppel-like factors (KLF) and specificity proteins (SP) are an important family of transcription factors (SP/KLF family) under extensive research [1,2,3]
We propose that KLF18 retrotransposition and local gene duplication resulted in further expansion of KLF members in the murine genomes of mouse and rat, giving rise to the highly diversified Zfp352, Zfp352l, and Zfp353 genes [15]
We selected a set of SP/KLF proteins consisting of known human KLF proteins (KLF1-KLF17) and SP proteins (SP1–SP9), three non-mammalian KLF17s, three predicted KLF18s, mouse and rat Zfp352 proteins and their close homologs, and the human Wilms’ tumor protein (WT1) as an out-group (WT1 contains four zinc fingers, three of which exhibit the same pattern as SP/KLF members and have a similar set of DNAbinding specificity residues as SP/KLF proteins)
Summary
Krüppel-like factors (KLF) and specificity proteins (SP) are an important family of transcription factors (SP/KLF family) under extensive research [1,2,3]. The most recent mammalian gene assigned to the SP/KLF family, KLF17 [10], was first discovered as a germ cell-specific gene encoding zinc finger protein 393 (Zfp393) in mouse [11].
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