Cole, Sharon Margaret; (1998) Tissue specific expression of serum amyloid A. Doctoral thesis (Ph.D), UCL (University College London).

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Abstract

The human serum amyloid A family of proteins is comprised of two acute phase proteins (SAA1 and SAA2) and one constitutively expressed protein (SAA4). The SAAs are predominantly produced by the liver although, some extra hepatic expresion has been reported. Liver specific of other proteins, such α-1 antitrypsin, is due to the presence of multiple binding sites for transcription factors which are predominantly but not exclusively expressed in the liver known as liver enriched transcription factor. C/EBP, which is known to transcriptionally regulate SAA expression, is one such Factors. Luciferase reporter constructs containing varying lengths of the 5' flanking regions of SAA2 were transfected into hepatic and non-hepatic cell lines. The results indicated that in addition to the C/EBP site a tissue specific element was also present between -2213bp and -2355bp. This fragment was subsequently shown to bind both a ubiquitously expressed nuclear factor and a liver specific factor. Sequence analysis identified consensuus binding sequences for a number of transcription factors including the factor YY1 which is involved in the transcriptional regulation of the rat SAA1 gene. Mutation of the YY1 consensus sequence caused a shift in the protein binding pattern observed in electrophoretic mobility shift assays. Preliminary analysis of the 5' flanking region of SAA4 has identified a C/EBP site at position -57bp. These results indicate that as with other liver specific proteins tissues specific expression of SAA is due to multiple elements incuding C/EBP an, in SAA2, an as of yet unidentified element of which the ubiquitously expressed transcription factor YY1 may be a component.

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