HSF4 is required for normal cell growth and differentiation during mouse lens development
Copyright policy )HSF4 is required for normal cell growth and differentiation during mouse lens development
The heat shock transcription factor (HSF) family consists of three members in mammals and regulates expression of heat shock genes via a heat shock element. HSF1 and HSF2 are required for some developmental processes, but it is unclear how they regulate these processes. To elucidate the mechanisms of developmental regulation by HSFs, we generated mice in which the HSF4 gene is mutated. HSF4-null mice had cataract with abnormal lens fiber cells containing inclusion-like structures, probably due to decreased expression of gamma-crystallin, which maintains protein stability. Furthermore, we found increased proliferation and premature differentiation of the mutant lens epithelial cells, which is associated with increased expression of growth factors, FGF-1, FGF-4, and FGF-7. Unexpectedly, HSF1 competed with HSF4 for the expression of FGFs not only in the lens but also in other tissues. These findings reveal the lens-specific role of HSF4, which activates gamma-crystallin genes, and also indicate that HSF1 and HSF4 are involved in regulating expression of growth factor genes, which are essential for cell growth and differentiation.
- Kyoto University Japan
- Yamaguchi University Japan
- RIKEN Center for Biosystems Dynamics Research Japan
- Aichi Human Service Center Japan
Inclusion Bodies, Mice, Knockout, Base Sequence, Molecular Sequence Data, Gene Expression Regulation, Developmental, Cell Differentiation, Epithelial Cells, DNA-Binding Proteins, Fibroblast Growth Factors, Mice, Heat Shock Transcription Factors, Gene Targeting, Lens, Crystalline, Animals, Humans, Protein Isoforms, Heat-Shock Proteins, Cell Proliferation, Protein Binding, Transcription Factors
Inclusion Bodies, Mice, Knockout, Base Sequence, Molecular Sequence Data, Gene Expression Regulation, Developmental, Cell Differentiation, Epithelial Cells, DNA-Binding Proteins, Fibroblast Growth Factors, Mice, Heat Shock Transcription Factors, Gene Targeting, Lens, Crystalline, Animals, Humans, Protein Isoforms, Heat-Shock Proteins, Cell Proliferation, Protein Binding, Transcription Factors
citations This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).221 popularity This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.Top 1% influence This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).Top 10% impulse This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.Top 10%
Citations provided by BIP!Popularity provided by BIP!