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Title: Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization

Abstract

Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are requiredmore » for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.« less

Authors:
; ;
Publication Date:
OSTI Identifier:
22594283
Resource Type:
Journal Article
Journal Name:
Biochemical and Biophysical Research Communications
Additional Journal Information:
Journal Volume: 471; Journal Issue: 4; Other Information: Copyright (c) 2016 Elsevier Science B.V., Amsterdam, The Netherlands, All rights reserved.; Country of input: International Atomic Energy Agency (IAEA); Journal ID: ISSN 0006-291X
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; DNA; ELECTROPHORESIS; GENES; HETEROCHROMATIN; HISTONES; LEUKEMIA; LEUKEMIA VIRUSES; METHYLATION; NUCLEOSOMES; ORGANIC FLUORINE COMPOUNDS; PHOSPHORYLATION; POLYVINYLS; THREONINE; ZINC

Citation Formats

Ichida, Yu, E-mail: ichida-y@ncchd.go.jp, Utsunomiya, Yuko, and Onodera, Masafumi. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization. United States: N. p., 2016. Web. doi:10.1016/J.BBRC.2016.02.040.
Ichida, Yu, E-mail: ichida-y@ncchd.go.jp, Utsunomiya, Yuko, & Onodera, Masafumi. Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization. United States. doi:10.1016/J.BBRC.2016.02.040.
Ichida, Yu, E-mail: ichida-y@ncchd.go.jp, Utsunomiya, Yuko, and Onodera, Masafumi. Fri . "Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization". United States. doi:10.1016/J.BBRC.2016.02.040.
@article{osti_22594283,
title = {Effect of the linkers between the zinc fingers in zinc finger protein 809 on gene silencing and nuclear localization},
author = {Ichida, Yu, E-mail: ichida-y@ncchd.go.jp and Utsunomiya, Yuko and Onodera, Masafumi},
abstractNote = {Zinc finger protein 809 (ZFP809) belongs to the Kruppel-associated box-containing zinc finger protein (KRAB-ZFP) family and functions in repressing the expression of Moloney murine leukemia virus (MoMLV). ZFP809 binds to the primer-binding site (PBS)located downstream of the MoMLV-long terminal repeat (LTR) and induces epigenetic modifications at integration sites, such as repressive histone modifications and de novo DNA methylation. KRAB-ZFPs contain consensus TGEKP linkers between C2H2 zinc fingers. The phosphorylation of threonine residues within linkers leads to the inactivation of zinc finger binding to target sequences. ZFP809 also contains consensus linkers between zinc fingers. However, the function of ZFP809 linkers remains unknown. In the present study, we constructed ZFP809 proteins containing mutated linkers and examined their ability to silence transgene expression driven by MLV, binding ability to MLV PBS, and cellular localization. The results of the present study revealed that the linkers affected the ability of ZFP809 to silence transgene expression. Furthermore, this effect could be partly attributed to changes in the localization of ZFP809 proteins containing mutated linkers. Further characterization of ZFP809 linkers is required for understanding the functions and features of KRAB-ZFP-containing linkers. - Highlights: • ZFP809 has three consensus linkers between the zinc fingers. • Linkers are required for ZFP809 to silence transgene expression driven by MLV-LTR. • Linkers affect the precise nuclear localization of ZFP809.},
doi = {10.1016/J.BBRC.2016.02.040},
journal = {Biochemical and Biophysical Research Communications},
issn = {0006-291X},
number = 4,
volume = 471,
place = {United States},
year = {2016},
month = {3}
}