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 hsbp 1 gene and examined zebrafish embryos treated with HSBP1-specific morpholino oligonucleotides. Our results show that hsbp 1 is critical for preimplantation embryonic development. Embryonic stem (ES) cells deficient in hsbp 1 survive and proliferate normally into the neural lineage in vitro ; however, lack of hsbp 1 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 hsbp 1-deficient mouse EBs and knockdown of HSBP1 in zebrafish leads to an increase in the expression of the neural crest inducers Snail 2, Tfap 2 α and Foxd 3, suggesting a potential role for HSBP1 in the Wnt pathway. The hsbp 1 - 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.