The third to fifth zinc fingers play an essential role in the binding of ZFP809 to the MLV-derived PBS

Yu, I.; Utsunomiya, Yuko; Onodera, Masafumi

doi:10.1016/j.bbrc.2015.12.029

Cited by 5 publications

(5 citation statements)

References 21 publications

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“…It has been shown to inhibit the transcriptional expression of MoMLV and is required for the silencing of endogenous retroviruses (ERVs) during mouse embryonic development [1,11]. Furthermore, domains with diverse functions have been shown within ZFP809 [12,13]. Here we discuss the functions and features of functional domains within ZFP809 in light of the findings of recent studies.…”

Section: Introductionmentioning

confidence: 87%

“…binding to the PBS. We investigated subcellular localization, gene silencing ability, and binding ability to the MLV-PBS using a series of truncated and mutated ZFP809 proteins [12,13]. We revealed that the KRAB domain is required for nuclear localization and silencing of transgene expression driven by the MLV-LTR and bind to the MLV-PBS in conjunction with the zinc fingers (Figure 1B) [12,13].…”

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

“…We investigated subcellular localization, gene silencing ability, and binding ability to the MLV-PBS using a series of truncated and mutated ZFP809 proteins [12,13]. We revealed that the KRAB domain is required for nuclear localization and silencing of transgene expression driven by the MLV-LTR and bind to the MLV-PBS in conjunction with the zinc fingers (Figure 1B) [12,13]. Although 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, particularly 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).…”

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

“…We revealed that the KRAB domain is required for nuclear localization and silencing of transgene expression driven by the MLV-LTR and bind to the MLV-PBS in conjunction with the zinc fingers (Figure 1B) [12,13]. Although 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, particularly 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). According to previous studies, ZFP809 interacts with regions within the MLV-PBS (underlined sequence) and does not recognize threenucleotide sequences, indicating that not all zinc fingers are necessarily involved in target DNA binding [21][22][23][24].…”

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

See 3 more Smart Citations

Functional and Structural Features of Zinc Finger Protein 809

Yu¹,

Utsunomiya²,

Onodera³

2016

Biochem Mol Biol J

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Section: Introductionmentioning

confidence: 87%

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

Section: Biochemistry and Molecular Biology Journal Issn 2471-8084mentioning

confidence: 99%

See 2 more Smart Citations

Functional and Structural Features of Zinc Finger Protein 809

Yu¹,

Utsunomiya²,

Onodera³

2016

Biochem Mol Biol J

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“…Currently, it is extremely challenging to predict the DNA-binding specificity (a combination of individual ZnFs) of a given KRAB-ZFP due to the following limitations [ 22 , 23 ]. 1) For a certain ZnF, its preferably bound DNA triplets in live cells cannot be predicted accurately [ 24 ]. It has been found that besides those “fingerprint” amino acids, other nearby amino acids including the linker sequences also contribute to the DNA binding activity [ 17 , 18 , 25 ].…”

Section: Introductionmentioning

confidence: 99%

Exploration of the regulatory relationship between KRAB-Zfp clusters and their target transposable elements via a gene editing strategy at the cluster specific linker-associated sequences by CRISPR-Cas9

Zhang

et al. 2022

Mobile DNA

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Background Krüppel Associated Box-containing Zinc Finger Proteins (KRAB-ZFPs), representing the largest superfamily of transcription factors in mammals, are predicted to primarily target and repress transposable elements (TEs). It is challenging to dissect the distinct functions of these transcription regulators due to their sequence similarity and diversity, and also the complicated repetitiveness of their targeting TE sequences. Results Mouse KRAB-Zfps are mainly organized into clusters genomewide. In this study, we revealed that the intra-cluster members had a close evolutionary relationship, and a similar preference for zinc finger (ZnF) usage. KRAB-Zfps were expressed in a cell type- or tissue type specific manner and they tended to be actively transcribed together with other cluster members. Further sequence analyses pointed out the linker sequences in between ZnFs were conserved, and meanwhile had distinct cluster specificity. Based on these unique characteristics of KRAB-Zfp clusters, sgRNAs were designed to edit cluster-specific linkers to abolish the functions of the targeted cluster(s). Using mouse embryonic stem cells (mESC) as a model, we screened and obtained a series of sgRNAs targeting various highly expressed KRAB-Zfp clusters. The effectiveness of sgRNAs were verified in a reporter assay exclusively developed for multi-target sgRNAs and further confirmed by PCR-based analyses. Using mESC cell lines inducibly expressing Cas9 and these sgRNAs, we found that editing different KRAB-Zfp clusters resulted in the transcriptional changes of distinct categories of TEs. Conclusions Collectively, the intrinsic sequence correlations of intra-cluster KRAB-Zfp members discovered in this study suggest that the conserved cluster specific linkers played crucial roles in diversifying the tandem ZnF array and the related target specificity of KRAB-Zfps during clusters’ evolution. On this basis, an effective CRISPR-Cas9 based approach against the linker sequences is developed and verified for rapidly editing KRAB-Zfp clusters to identify the regulatory correlation between the cluster members and their potential TE targets.

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The role of zinc and its compounds in leukemia

et al. 2018

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Zinc is one of the most important microelements necessary for normal body functioning. Zinc is marked in numerous diseases and, hence, its properties and behavior in the body have long been a subject of extensive study. This review considers trends in the assessment of the role of zinc and its compounds in the past decade. It becomes evident that redox-inactive zinc is the main supervisor in the conformation of the most important molecules in all body organs and tissues. We placed emphasis on the variety of zinc-binding sites and the role of zinc in the genesis and progress of different forms of leukemia. The importance of some families of transcription factors in the development and prognosis of treatment of various leukemia forms is examined; new directions of these studies are shown.

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The third to fifth zinc fingers play an essential role in the binding of ZFP809 to the MLV-derived PBS

Cited by 5 publications

References 21 publications

Functional and Structural Features of Zinc Finger Protein 809

Functional and Structural Features of Zinc Finger Protein 809

Exploration of the regulatory relationship between KRAB-Zfp clusters and their target transposable elements via a gene editing strategy at the cluster specific linker-associated sequences by CRISPR-Cas9

The role of zinc and its compounds in leukemia

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