Abstract
Abstract: :
Purpose: There are three known mammalian heat shock transcription factors (HSFs) HSF1, HSF2 and HSF4. The ubiquitous HSF1 is known to respond to stress, while HSF2 has been associated with developmental regulation. A mutation in HSFF4 has recently been shown to be associated with cataractogenesis. We have previously shown that HSF interaction with the canonical heat shock promoter of alpha B-crystallin gene is developmentally regulated in a tissue-specific fashion. The present investigation was conducted to identify the HSFs and their inter-relationship(s) in transcription activation/repression in the developing and postnatal lens. Methods: We have used cell fractionation coupled with FPLC, gel-mobility-shift-assays, two-dimensional polyacrylamide gel electrophoresis and RT-PCR to characterize the presence and developmental expression of HSFs and their isoforms in the rat lens. Results All the mammalian heat shock factors are expressed in the ocular lens in a stage-specific pattern. It was interesting to note that HSF1 ( the stress associated HSF) and HSF2 are predominant in the fetal lens, while HSF4 is predominant in the postnatal adult lens. Comparative analyses done with ten different rat tissues revealed that among HSFs, HSF4 is maximally expressed in the lens.Within the adult lens HSF4 seems to be the predominant HSF. Conclusions: The dynamics of the expression of the HSFs suggests their significant involvement in regulating gene expression in the lens, particularly in the context of expression of heat shock genes (such as alpha B-crystallin, with highly active postnatal transcription). The predominant presence of HSF4 in the lens may have important implication in the maintenance transparency in light of the recently reported association of mutant HSF4 and cataractogenesis.
Keywords: gene/expression • transcription factors • molecular biology