Cargando…

Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response

Interferon regulatory factors (IRFs) constitute a family of transcription factors that synchronize interferon (IFN) antiviral response through translocating to nucleus and binding to the promoters of IFN and IFN-stimulated genes (ISGs). Fish contain 11 IRF members; however, whether or how fish IRF f...

Descripción completa

Detalles Bibliográficos
Autores principales: An, Li-Li, Zhao, Xiang, Gong, Xiu-Ying, Li, Yi-Lin, Qu, Zi-Ling, Sun, Hao-Yu, Guo, Wen-Hao, Dan, Cheng, Gui, Jian-Fang, Zhang, Yi-Bing
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019167/
https://www.ncbi.nlm.nih.gov/pubmed/35464458
http://dx.doi.org/10.3389/fimmu.2022.861262
_version_ 1784689195318509568
author An, Li-Li
Zhao, Xiang
Gong, Xiu-Ying
Li, Yi-Lin
Qu, Zi-Ling
Sun, Hao-Yu
Guo, Wen-Hao
Dan, Cheng
Gui, Jian-Fang
Zhang, Yi-Bing
author_facet An, Li-Li
Zhao, Xiang
Gong, Xiu-Ying
Li, Yi-Lin
Qu, Zi-Ling
Sun, Hao-Yu
Guo, Wen-Hao
Dan, Cheng
Gui, Jian-Fang
Zhang, Yi-Bing
author_sort An, Li-Li
collection PubMed
description Interferon regulatory factors (IRFs) constitute a family of transcription factors that synchronize interferon (IFN) antiviral response through translocating to nucleus and binding to the promoters of IFN and IFN-stimulated genes (ISGs). Fish contain 11 IRF members; however, whether or how fish IRF family genes function in IFN response remains limited. Herein, we determine the regulatory roles of 11 zebrafish IRF family members in IFN response relevant to their subcellular localization and promoter binding. Zebrafish IRF family members display three patterns of constitutive localization, only in nucleus (IRF1/2/9/11), only in cytoplasm (IRF3/5/7), and largely in nucleus with small amounts in cytoplasm (IRF4b/6/8/10). DNA pull-down assays confirm that all zebrafish IRF proteins are capable to bind fish IFN promoters, albeit to various degrees, thus regulating IFN gene transcription as activators (IRF1/3/5/6/7/8/9/11) or repressors (IRF2/4b/10). Further characterization of distinct IFN gene activation reveals that IRF1/3/5/6/7/8/9/11 efficiently stimulate zebrafish IFNφ1 expression, and IRF1/7/11 are responsible for zebrafish IFNφ3 expression. Two conserved basic residues within the helix α3 of DNA binding domains (DBDs) contribute to constitutive or inducible nuclear import for all zebrafish IRF family members and DNA binding for most members, thereby enabling them to function as transcription factors. Our results reveal a conserved and general mechanism that specifies zebrafish IRF family proteins to nuclear import and DNA binding, thereby regulating fish IFN response.
format Online
Article
Text
id pubmed-9019167
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Frontiers Media S.A.
record_format MEDLINE/PubMed
spelling pubmed-90191672022-04-21 Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response An, Li-Li Zhao, Xiang Gong, Xiu-Ying Li, Yi-Lin Qu, Zi-Ling Sun, Hao-Yu Guo, Wen-Hao Dan, Cheng Gui, Jian-Fang Zhang, Yi-Bing Front Immunol Immunology Interferon regulatory factors (IRFs) constitute a family of transcription factors that synchronize interferon (IFN) antiviral response through translocating to nucleus and binding to the promoters of IFN and IFN-stimulated genes (ISGs). Fish contain 11 IRF members; however, whether or how fish IRF family genes function in IFN response remains limited. Herein, we determine the regulatory roles of 11 zebrafish IRF family members in IFN response relevant to their subcellular localization and promoter binding. Zebrafish IRF family members display three patterns of constitutive localization, only in nucleus (IRF1/2/9/11), only in cytoplasm (IRF3/5/7), and largely in nucleus with small amounts in cytoplasm (IRF4b/6/8/10). DNA pull-down assays confirm that all zebrafish IRF proteins are capable to bind fish IFN promoters, albeit to various degrees, thus regulating IFN gene transcription as activators (IRF1/3/5/6/7/8/9/11) or repressors (IRF2/4b/10). Further characterization of distinct IFN gene activation reveals that IRF1/3/5/6/7/8/9/11 efficiently stimulate zebrafish IFNφ1 expression, and IRF1/7/11 are responsible for zebrafish IFNφ3 expression. Two conserved basic residues within the helix α3 of DNA binding domains (DBDs) contribute to constitutive or inducible nuclear import for all zebrafish IRF family members and DNA binding for most members, thereby enabling them to function as transcription factors. Our results reveal a conserved and general mechanism that specifies zebrafish IRF family proteins to nuclear import and DNA binding, thereby regulating fish IFN response. Frontiers Media S.A. 2022-04-06 /pmc/articles/PMC9019167/ /pubmed/35464458 http://dx.doi.org/10.3389/fimmu.2022.861262 Text en Copyright © 2022 An, Zhao, Gong, Li, Qu, Sun, Guo, Dan, Gui and Zhang https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Immunology
An, Li-Li
Zhao, Xiang
Gong, Xiu-Ying
Li, Yi-Lin
Qu, Zi-Ling
Sun, Hao-Yu
Guo, Wen-Hao
Dan, Cheng
Gui, Jian-Fang
Zhang, Yi-Bing
Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title_full Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title_fullStr Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title_full_unstemmed Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title_short Promoter Binding and Nuclear Retention Features of Zebrafish IRF Family Members in IFN Response
title_sort promoter binding and nuclear retention features of zebrafish irf family members in ifn response
topic Immunology
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9019167/
https://www.ncbi.nlm.nih.gov/pubmed/35464458
http://dx.doi.org/10.3389/fimmu.2022.861262
work_keys_str_mv AT anlili promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT zhaoxiang promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT gongxiuying promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT liyilin promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT quziling promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT sunhaoyu promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT guowenhao promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT dancheng promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT guijianfang promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse
AT zhangyibing promoterbindingandnuclearretentionfeaturesofzebrafishirffamilymembersinifnresponse