Functional and Structural Features of Zinc Finger Protein 809

Yu Ichida,Yuko Utsunomiya,Masafumi Onodera

doi:10.21767/2471-8084.100010

Abstract

Zinc finger protein 809 (ZFP809) is a member of the kruppel-associated boxcontaining ZFP (KRAB-ZFP) family. It supresses the expression of Moloney murine leukemia virus (MoMLV) via sequence-specific binding to the primer binding site (PBS) located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at the LTR, such as repressive histone modifications and de novo DNA methylation. Recent studies have demonstrated the features of diverse functional domains of ZFP809, which has a KRAB domain and seven zinc fingers. We previously demonstrated that the KRAB domain is essential for nuclear localization, gene silencing, and binding to the MLV-PBS in conjunction with the accessory roles of a subset of zinc fingers. Individual zinc fingers are known to contribute to binding to the MLV-PBS and stable protein expression. Furthermore, the mechanisms underlying the high expression of ZFP809 in immature cells have yet to be fully elucidated. Recent studies have indicated that ZFP809 is stably expressed in immature cells, such as embryonic stem cells (ESCs), as ESCs have higher expression of KRAB-associated protein 1 (KAP1) than mature mouse embryonic fibroblast cells. Here we discuss the ZFP809/KAP1 complex, functional domains of ZFP809, and expression pattern of ZFP809 in immature cells.

Highlights

In 2009, Wolf and Goff [1] revealed that zinc finger protein 809 (ZFP809) has a central role in the transcriptional suppression of Moloney murine leukemia virus (MoMLV)
We revealed that the KRAB domain is required for nuclear localization and silencing of transgene expression driven by the MLV-long terminal repeat (LTR) and bind to the MLV-primer binding site (PBS) in conjunction with the zinc fingers (Figure 1B) [12,13]
Previous studies have indicated that zinc fingers within KRAB-ZFPs bind to specific DNA sequences and directly interact with three-nucleotide sequences [3,10], our results demonstrated that individual zinc fingers, the third, fourth, and fifth zinc fingers, are required for the binding of ZFP809 to the MLV-PBS and that other zinc fingers contribute to stable protein expression [12,13] (Figure 1B)

Summary

Introduction

In 2009, Wolf and Goff [1] revealed that zinc finger protein 809 (ZFP809) has a central role in the transcriptional suppression of Moloney murine leukemia virus (MoMLV). Previous studies have demonstrated that the ZFP809/KAP1 complex recruits heterochromatin protein 1, an ERG-associated protein with a SET domain (ESET, a H3K9 methyltransferase), the nucleosome remodeling and deacetylation complex including histone deacetylation 1 (HDAC1), and DNA methyltransferase 3A (DNMT3A).

Results

Conclusion