title: An essential role for heat shock transcription factor binding protein 1 (HSBP1) during early embryonic development.
abstract: Heat shock factor binding protein 1 (HSBP1) is a 76 amino acid polypeptide that contains two arrays of hydrophobic heptad repeats and was originally identified through its interaction with the oligomerization domain of heat shock factor 1 (Hsf1), suppressing Hsf1's transcriptional activity following stress. To examine the function of HSBP1 in vivo, we generated mice with targeted disruption of the hsbp1 gene and examined zebrafish embryos treated with HSBP1-specific morpholino oligonucleotides. Our results show that hsbp1 is critical for preimplantation embryonic development. Embryonic stem (ES) cells deficient in hsbp1 survive and proliferate normally into the neural lineage in vitro; however, lack of hsbp1 in embryoid bodies (EBs) leads to disorganization of the germ layers and a reduction in the endoderm-specific markers (such as α-fetoprotein). We further show that hsbp1-deficient mouse EBs and knockdown of HSBP1 in zebrafish leads to an increase in the expression of the neural crest inducers Snail2, Tfap2α and Foxd3, suggesting a potential role for HSBP1 in the Wnt pathway. The hsbp1-deficient ES cells, EBs and zebrafish embryos with reduced HSBP1 levels exhibit elevated levels of Hsf1 activity and expression of heat shock proteins (Hsps). We conclude that HSBP1 plays an essential role during early mouse and zebrafish embryonic development.
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA 30904, United States; Chaperone Biology, Georgia Regents University (GRU) Cancer Center, Medical College of Georgia (MCG), 1120 15th St., Augusta, GA 30912, United States.
authors.forename: Binnur
authors.initials: B
authors.lastname: Eroglu
authors.affiliation: Chaperone Biology, Georgia Regents University (GRU) Cancer Center, Medical College of Georgia (MCG), 1120 15th St., Augusta, GA 30912, United States. Electronic address: jin-na.min@yale.edu.
authors.forename: Jin-Na
authors.initials: JN
authors.lastname: Min
authors.affiliation: Chaperone Biology, Georgia Regents University (GRU) Cancer Center, Medical College of Georgia (MCG), 1120 15th St., Augusta, GA 30912, United States. Electronic address: yanzhang@vt.edu.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Institute of Molecular Medicine and Genetics, GRU, MCG, GA, United States.
authors.forename: Edyta
authors.initials: E
authors.lastname: Szurek
authors.affiliation: Chaperone Biology, Georgia Regents University (GRU) Cancer Center, Medical College of Georgia (MCG), 1120 15th St., Augusta, GA 30912, United States.
authors.forename: Demetrius
authors.initials: D
authors.lastname: Moskophidis
authors.affiliation: Institute of Molecular Medicine and Genetics, GRU, MCG, GA, United States. Electronic address: Aeroglu@gru.edu.
authors.forename: Ali
authors.initials: A
authors.lastname: Eroglu
authors.affiliation: Charlie Norwood VA Medical Center, One Freedom Way, Augusta, GA 30904, United States; Chaperone Biology, Georgia Regents University (GRU) Cancer Center, Medical College of Georgia (MCG), 1120 15th St., Augusta, GA 30912, United States. Electronic address: nmivechi@gru.edu.
authors.forename: Nahid F
authors.initials: NF
authors.lastname: Mivechi
mesh_terms: D000818:Animals; D015153:Blotting, Western; D004268:DNA-Binding Proteins / Q000378:metabolism; D058732:Embryoid Bodies / Q000378:metabolism; D047108:Embryonic Development / Q000502:physiology*; D004707:Endoderm / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology*; D005838:Genotype; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism*; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D051379:Mice; D018832:Molecular Chaperones; D060172:Morpholinos / Q000235:genetics; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism*; D009432:Neural Crest / Q000196:embryology*; D060888:Real-Time Polymerase Chain Reaction; D014157:Transcription Factors / Q000378:metabolism; D060449:Wnt Signaling Pathway / Q000235:genetics; D015027:Zebrafish; D000509:alpha-Fetoproteins / Q000378:metabolism
chemical_list: D004268:DNA-Binding Proteins; D000076249:Heat Shock Transcription Factors; D006360:Heat-Shock Proteins; C486113:Hsbp1 protein, mouse; C490017:Hsf1 protein, mouse; D018832:Molecular Chaperones; D060172:Morpholinos; D009363:Neoplasm Proteins; D014157:Transcription Factors; D000509:alpha-Fetoproteins
keywords: Embryonic stem cells; HSBP1; Knockout mice; Neural crest; Zebrafish