Multiple tissue-specific promoters control expression of the murine tartrate-resistant acid phosphatase gene.
Tartrate-resistant acid phosphatase (TRAP) is highly expressed in osteoclasts and in a subset of tissue macrophages and dendritic cells. It is expressed at lower levels in the parenchymal cells of the liver, glomerular mesangial cells of the kidney and pancreatic acinar cells. We have identified novel TRAP mRNAs that differ in their 5'-untranslated region (5'-UTR) sequence, but align with the known murine TRAP mRNA from the first base of Exon 2. The novel 5'-UTRs represent alternative first exons located upstream of the known 5'-UTR. A similar genomic structure exists for the human TRAP gene with partial conservation of the exon and promoter sequences. Expression of the most distal 5'-UTR (Exon 1A) is restricted to adult bone and spleen tissue. Exon 1B is expressed primarily in tissues containing TRAP-positive non-haematopoietic cells. The known TRAP 5'-UTR (Exon 1C) is expressed in tissues characteristic of myeloid cell expression. In addition the Exon 1C promoter sequence is shown to comprise distinct transcription start regions, with an osteoclast-specific transcription initiation site identified downstream of a TATA-like element. Macrophages are shown to initiate transcription of the Exon 1C transcript from a purine-rich region located upstream of the osteoclast-specific transcription start point. The distinct expression patterns for each of the TRAP 5'-UTRs suggest that TRAP mRNA expression is regulated by the use of four alternative tissue- and cell-restricted promoters.
Walsh
Nicole C
NC
Institute for Molecular Bioscience and School of Molecular and Microbial Sciences, University of Queensland, Brisbane, Australia.
Cahill
Marian
M
Carninci
Piero
P
Kawai
Jun
J
Okazaki
Yasushi
Y
Hayashizaki
Yoshihide
Y
Hume
David A
DA
Cassady
A Ian
AI
D020121:5' Untranslated Regions / Q000235:genetics; D000135:Acid Phosphatase / Q000235:genetics*; D017398:Alternative Splicing; D000818:Animals; D001483:Base Sequence; D002478:Cells, Cultured; D005091:Exons; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D005796:Genes / Q000235:genetics; D006801:Humans; D007438:Introns; D007527:Isoenzymes / Q000235:genetics*; D051379:Mice; D008807:Mice, Inbred BALB C; D008809:Mice, Inbred C3H; D008810:Mice, Inbred C57BL; D008811:Mice, Inbred DBA; D008815:Mice, Inbred Strains; D008969:Molecular Sequence Data; D011401:Promoter Regions, Genetic / Q000235:genetics*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012689:Sequence Homology, Nucleic Acid; D000071681:Tartrate-Resistant Acid Phosphatase; D024363:Transcription Initiation Site; D014158:Transcription, Genetic
D020121:5' Untranslated Regions; D007527:Isoenzymes; D012333:RNA, Messenger; D000135:Acid Phosphatase; C000605511:Acp5 protein, mouse; D000071681:Tartrate-Resistant Acid Phosphatase