KRAB-Zinc Finger Proteins: A Repressor Family Displaying Multiple Biological Functions

Angelo Lupo,Elena Cesaro,Paola Izzo,Diana Zurlo,Paola Costanzo,Giorgia Montano

doi:10.2174/13892029113149990002

Angelo Lupo, Elena Cesaro + Show 4 more

Open Access

https://doi.org/10.2174/13892029113149990002

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Abstract

Zinc finger proteins containing the Kruppel associated box (KRAB-ZFPs) constitute the largest individual family of transcriptional repressors encoded by the genomes of higher organisms. KRAB domain, positioned at the NH2 terminus of the KRAB-ZFPs, interacts with a scaffold protein, KAP-1, which is able to recruit various transcriptional factors causing repression of genes to which KRAB ZFPs bind. The relevance of such repression is reflected in the large number of the KRAB zinc finger protein genes in the human genome. However, in spite of their numerical abundance little is currently known about the gene targets and the physiological functions of KRAB- ZFPs. However, emerging evidence links the transcriptional repression mediated by the KRAB-ZFPs to cell proliferation, differentiation, apoptosis and cancer. Moreover, the fact that KRAB containing proteins are vertebrate-specific suggests that they have evolved recently, and that their key roles lie in some aspects of vertebrate development. In this review, we will briefly discuss some regulatory functions of the KRAB-ZFPs in different physiological and pathological states, thus contributing to better understand their biological roles.

Highlights

Transcriptional control in eukaryotic cells is an extremely complex process involving a large number of transcription factors (TFs) and cofactors that regulate the assembly of transcription-initiation complexes and the rate at which transcription is initiated
Comparison between homologous clusters from human chromosome 19 (HAS 19q13.2) and mouse chromosome 7 (Mmu7) confirmed that human KRAB-ZFPs differed from their mouse counterparts in both the number of zinc finger domains and the sequences, suggesting that the divergence between the species might have resulted from a dramatic difference in DNA-binding properties [27]
By a genome-wide ChIP-sequencing approach, more than 5000 binding sites for ZNF263 were identified in K562 cells and many of the ZNF263 target genes were found to be positively regulated by ZNF263 [51], further supporting the idea that KRAB-ZFPs can have both positive and negative effects on transcription

Summary

Introduction

Transcriptional control in eukaryotic cells is an extremely complex process involving a large number of transcription factors (TFs) and cofactors that regulate the assembly of transcription-initiation complexes and the rate at which transcription is initiated. C2H2 zinc finger proteins contain from 1 to more than 30 ZF motifs and represent the largest family of regulatory proteins in mammals, involved in transcriptional regulation through the binding of their sequence-specific DNA binding motifs to the promoter regions of the genes.

Results

Conclusion