Endogenous retroviral sequences are required for tissue-specific expression of a human salivary amylase gene.
The human salivary amylase genes are associated with two inserted elements, a gamma-actin-processed pseudogene and an endogenous retroviral-like element. To test the contribution of these inserted elements to tissue specificity, 25 lines of transgenic mice carrying 10 amylase constructs were established. A 1-kb fragment of AMY1C (-1003 to +2) was found to be sufficient for parotid-specific expression of a human growth hormone reporter gene. The 1-kb fragment is entirely derived from inserted sequences. Deletion from -1003 to -826 resulted in reduced levels of transgene expression and loss of tissue specificity. The fragment -1003 to -327 was sufficient to transfer parotid specificity to the thymidine kinase promoter. The data demonstrate that the functional tissue-specific promoter of human AMY1C is derived from inserted sequences and that parotid expression can be conferred by sequences derived solely from the retrovirus. A role for retrotransposition in the evolution of gene regulation is indicated by these and other recent observations.
Ting
C N
CN
Department of Human Genetics, University of Michigan, Ann Arbor 48109-0618.
Rosenberg
M P
MP
Snow
C M
CM
Samuelson
L C
LC
Meisler
M H
MH
D000199:Actins / Q000235:genetics; D000681:Amylases / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D004251:DNA Transposable Elements / Q000235:genetics; D015967:Gene Expression Regulation, Viral / Q000235:genetics*; D013006:Growth Hormone / Q000235:genetics; D006801:Humans; D051379:Mice; D008822:Mice, Transgenic / Q000235:genetics*; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides / Q000235:genetics; D010306:Parotid Gland / Q000201:enzymology* / Q000382:microbiology; D016133:Polymerase Chain Reaction; D011401:Promoter Regions, Genetic / Q000235:genetics; D011533:Proviruses / Q000235:genetics*; D011863:Radioimmunoassay; D011993:Recombinant Fusion Proteins / Q000235:genetics; D014158:Transcription, Genetic / Q000235:genetics
D000199:Actins; D004251:DNA Transposable Elements; D009838:Oligodeoxyribonucleotides; D011993:Recombinant Fusion Proteins; D013006:Growth Hormone; D000681:Amylases