IHB OpenIR  > 水生生物分子与细胞生物学研究中心  > 期刊论文
HSF4 regulates DLAD expression and promotes lens de-nucleation
Cui, Xiukun1; Wang, Lei1; Zhang, Jing1,2; Du, Rong3; Liao, Shengjie1; Li, Duanzhuo1; Li, Chang1; Ke, Tie1; Li, David Wan-Cheng4,5; Huang, Hua6; Yin, Zhan2; Tang, Zhaohui1; Liu, Mugen1; Tang, ZH (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
2013-08-01
Source PublicationBIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE
ISSN0925-4439
Volume1832Issue:8Pages:1167-1172
AbstractHSF4 mutations lead to both congenital and age-related cataract. The purpose of this study was to explore the mechanism of cataract formation caused by HSF4 mutations. The degradation of nuclear DNA is essential for the lens fiber differentiation. DNase 2 beta (DLAD) is highly expressed in lens cells, and mice with deficiencies in the DLAD gene develop nuclear cataracts. In this study, we found that HSF4 promoted the expression and DNase activity of DIAD by directly binding to the DIAD promoter. In contrast, HSF4 cataract causative mutations failed to bind to the DLAD promoter, abrogating the expression and DNase activity of DLAD. These results were confirmed by HSF4 knockdown in zebrafish, which led to incomplete de-nucleation of the lens and decreased expression and activity of DLAD. Together, our results suggest that HSF4 exerts its function on lens differentiation via positive regulation of DIAD expression and activity, thus facilitating de-nucleation of lens fiber cells. Our demonstration that HSF4 cataract causative mutations abrogate the induction of DLAD expression reveals a novel molecular mechanism regarding how HSF4 mutations cause cataractogenesis. (C) 2013 Elsevier B.V. All rights reserved.; HSF4 mutations lead to both congenital and age-related cataract. The purpose of this study was to explore the mechanism of cataract formation caused by HSF4 mutations. The degradation of nuclear DNA is essential for the lens fiber differentiation. DNase 2 beta (DLAD) is highly expressed in lens cells, and mice with deficiencies in the DLAD gene develop nuclear cataracts. In this study, we found that HSF4 promoted the expression and DNase activity of DIAD by directly binding to the DIAD promoter. In contrast, HSF4 cataract causative mutations failed to bind to the DLAD promoter, abrogating the expression and DNase activity of DLAD. These results were confirmed by HSF4 knockdown in zebrafish, which led to incomplete de-nucleation of the lens and decreased expression and activity of DLAD. Together, our results suggest that HSF4 exerts its function on lens differentiation via positive regulation of DIAD expression and activity, thus facilitating de-nucleation of lens fiber cells. Our demonstration that HSF4 cataract causative mutations abrogate the induction of DLAD expression reveals a novel molecular mechanism regarding how HSF4 mutations cause cataractogenesis. (C) 2013 Elsevier B.V. All rights reserved.
SubtypeArticle
KeywordHsf4 Cataract Mutation Dlad Lens Differentiation
Department[Cui, Xiukun ; Wang, Lei ; Zhang, Jing ; Liao, Shengjie ; Li, Duanzhuo ; Li, Chang ; Ke, Tie ; Tang, Zhaohui ; Liu, Mugen] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Coll Life Sci & Technol, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China ; [Zhang, Jing ; Yin, Zhan] Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China ; [Du, Rong] Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China ; [Li, David Wan-Cheng] Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA ; [Li, David Wan-Cheng] Univ Nebraska Med Ctr, Coll Med, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA ; [Huang, Hua] Hubei Univ Nationalities, Affiliated Hosp, Enshi 445000, Hubei, Peoples R China
DOI10.1016/j.bbadis.2013.03.007
WOS HeadingsScience & Technology ; Life Sciences & Biomedicine
Funding OrganizationNational Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380]
Indexed BySCI
Language英语
WOS Research AreaBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS SubjectBiochemistry & Molecular Biology ; Biophysics ; Cell Biology
WOS IDWOS:000321081300007
WOS KeywordRECESSIVE CONGENITAL CATARACTS ; FIBER CELL-DIFFERENTIATION ; HEAT-SHOCK RESPONSE ; ALPHA-B-CRYSTALLIN ; MOUSE EYE LENS ; DNASE-II ; TRANSCRIPTION FACTOR ; MUTATION ; DEGRADATION ; FAMILY
Funding OrganizationNational Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380] ; National Natural Science Foundation of China [81270983, 31071106, 30771199]; National Key Technology R&D Program of China [2012BAI09B00]; NIH/NEI [1R01EY018380]
Citation statistics
Document Type期刊论文
Identifierhttp://ir.ihb.ac.cn/handle/342005/19612
Collection水生生物分子与细胞生物学研究中心_期刊论文
Corresponding AuthorTang, ZH (reprint author), Huazhong Univ Sci & Technol, Ctr Human Genome Res, 1037 Luoyu Rd, Wuhan 430074, Hubei, Peoples R China.
Affiliation1.Huazhong Univ Sci & Technol, Ctr Human Genome Res, Coll Life Sci & Technol, Key Lab Mol Biophys,Minist Educ, Wuhan 430074, Hubei, Peoples R China
2.Chinese Acad Sci, Inst Hydrobiol, Wuhan 430072, Hubei, Peoples R China
3.Huazhong Univ Sci & Technol, Union Hosp, Wuhan 430022, Hubei, Peoples R China
4.Univ Nebraska Med Ctr, Coll Med, Dept Biochem & Mol Biol, Omaha, NE 68198 USA
5.Univ Nebraska Med Ctr, Coll Med, Dept Ophthalmol & Visual Sci, Omaha, NE 68198 USA
6.Hubei Univ Nationalities, Affiliated Hosp, Enshi 445000, Hubei, Peoples R China
Recommended Citation
GB/T 7714
Cui, Xiukun,Wang, Lei,Zhang, Jing,et al. HSF4 regulates DLAD expression and promotes lens de-nucleation[J]. BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,2013,1832(8):1167-1172.
APA Cui, Xiukun.,Wang, Lei.,Zhang, Jing.,Du, Rong.,Liao, Shengjie.,...&Tang, ZH .(2013).HSF4 regulates DLAD expression and promotes lens de-nucleation.BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE,1832(8),1167-1172.
MLA Cui, Xiukun,et al."HSF4 regulates DLAD expression and promotes lens de-nucleation".BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR BASIS OF DISEASE 1832.8(2013):1167-1172.
Files in This Item:
File Name/Size DocType Version Access License
HSF4 regulates DLAD (988KB) 开放获取CC BY-NC-SAView Application Full Text
Related Services
Recommend this item
Bookmark
Usage statistics
Export to Endnote
Google Scholar
Similar articles in Google Scholar
[Cui, Xiukun]'s Articles
[Wang, Lei]'s Articles
[Zhang, Jing]'s Articles
Baidu academic
Similar articles in Baidu academic
[Cui, Xiukun]'s Articles
[Wang, Lei]'s Articles
[Zhang, Jing]'s Articles
Bing Scholar
Similar articles in Bing Scholar
[Cui, Xiukun]'s Articles
[Wang, Lei]'s Articles
[Zhang, Jing]'s Articles
Terms of Use
No data!
Social Bookmark/Share
File name: HSF4 regulates DLAD expression and promotes lens de-nucleation.pdf
Format: Adobe PDF
This file does not support browsing at this time
All comments (0)
No comment.
 

Items in the repository are protected by copyright, with all rights reserved, unless otherwise indicated.