title: Effect of HSF4b on age related cataract may through its novel downstream target Hif1α.
abstract: Our previous study identified five new heat shock factor 4 (HSF4) mutations in 150 age-related cataract (ARC) patients which indicated that HSF4 mutations may be associated with this disease. Hypoxia-inducible factor (Hif1α) is an important downstream target of HSF4b. It has been found that Hif1α play also important roles in cataract development. To identify if HSF4b play it role in cataract development through HIF1α, we transfected SRA01/04 lens epithelial cells with small hairpin RNA of HSF4b and measured expressions Hif1α after transfection. Then, we perform chromatin immunoprecipitation quantitative PCR to see the relationship between HSF4b and HIF1α. We found that HSF4 downregulation led to decrease of HIF1α mRNA expression. Furthermore, we demonstrated by ChIP followed by quantitative PCR (ChIP-qPCR) that these HIF-1α is bound by HSF4b near promoters, not gene bodies.
authors.affiliation: Department of Ophthalmology, Sixth People's Hospital Affiliated of Shanghai Jiaotong University, China; Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
authors.affiliation: Department of Ophthalmology, Sixth People's Hospital Affiliated of Shanghai Jiaotong University, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Aizhu
authors.initials: A
authors.lastname: Miao
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: Yongxiang
authors.initials: Y
authors.lastname: Jiang
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China.
authors.forename: XinHua
authors.initials: X
authors.lastname: Wu
authors.affiliation: State Key Lab of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Zhentian
authors.initials: Z
authors.lastname: Wang
authors.affiliation: State Key Lab of Genetic Engineering, Institute of Genetics, School of Life Science, Fudan University, Shanghai, China.
authors.forename: Feizhen
authors.initials: F
authors.lastname: Wu
authors.affiliation: Department of Ophthalmology, Eye and ENT Hospital of Fudan University, Shanghai, China. Electronic address: luyieent@126.com.
authors.forename: Yi
authors.initials: Y
authors.lastname: Lu
mesh_terms: D000375:Aging / Q000473:pathology*; D001483:Base Sequence; D002386:Cataract / Q000378:metabolism*; D002478:Cells, Cultured; D017931:DNA Primers; D004268:DNA-Binding Proteins / Q000378:metabolism*; D000076249:Heat Shock Transcription Factors; D006801:Humans; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000235:genetics / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic; D014157:Transcription Factors / Q000378:metabolism*; D014158:Transcription, Genetic
chemical_list: D017931:DNA Primers; D004268:DNA-Binding Proteins; C497442:HIF1A protein, human; C102948:HSF4 protein, human; D000076249:Heat Shock Transcription Factors; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D014157:Transcription Factors
keywords: Age-related cataract (ARC); Chromatin immunoprecipitation (ChIP); Heat shock factor 4b (HSF4b); Hypoxia-inducible factor (Hif1α); Small hairpin RNA