Genomic organization of the human catechol O‐methyltransferase gene and its expression from two distinct promoters
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Human genomic DNA fragments containing catechol O-methyltransferase (COMT) sequences were isolated and the exon-intron structure analysed by sequencing, PCR and comparing to the human COMT cDNA sequences. The gene contains six exons, of which exons 1 and 2 are noncoding. MB-ATG and S-ATG codons, responsible for the initiation of translation of the membrane-bound (MB) and soluble (S) forms of the enzyme, are located in exon 3. Two distinct COMT-specific transcripts, 1.3 kb and 1.5 kb, were detected in various human tissues and cell lines. Different quantities of the shorter COMT-specific mRNA in the tissues studied suggest a tissue-specific regulation of the COMT gene at transcriptional level. Mapping of the 5' ends of the COMT mRNAs showed that transcription initiates at multiple sites in two separate DNA regions, which are preceded by functional promoter sequences. The proximal promoter (P1), located between the two translation initiation codons and extending approximately 200 bp upstream of the MB-ATG initiation codon, apparently gives rise to the 1.3-kb S-COMT mRNA (S-mRNA). The distal promoter (P2) is located in a DNA fragment in front of and partly overlapping the transcription-start region of the 1.5-kb transcript, suggesting that it controls the expression of this MB-mRNA. Similarities between the rat and human COMT gene promoters are analyzed.
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The predominant form of COMT in peripheral tissue is the soluble isoform (S-COMT).
“The predominant form in peripheral tissue is the soluble isoform (S-COMT) [52].”
From Dynamic DNA methylation changes in the COMT gene promoter region in response to mental stress and its modulation by transcranial direct current stimulation (2021) · cites this paper as [52]
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- Authors
- TENHUNEN, J., SALMINEN, M., LUNDSTRÖM, K., KIVILUOTO, T., SAVOLAINEN, R., & ULMANEN, I.
- Affiliations
- Orion Corporation (Finland) (FI)
- Helsinki University Hospital (FI)
- Corresponding author
- TENHUNEN, Jukka
- ORCID
- SALMINEN, Marjo
- Venue
- European Journal of Biochemistry
- Publisher
- Wiley
- Published
- 1994-08
- Volume
- 223
- Issue
- 3
- Pages
- 1049-1059
- ISSN
- 0014-2956 (ISSN-L)
- 1432-1033
- OpenAlex
- W2135835694
- Cited by
- 331
- References
- 38
- Citations by year
- 2026: 6 · 2025: 2 · 2024: 1 · 2023: 7 · 2022: 7 · 2021: 7 · 2020: 6 · 2019: 13 · 2018: 2 · 2017: 6 · 2016: 15 · 2015: 4 · 2014: 14 · 2013: 16 · 2012: 12
- FWCI
- 7.31
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- European Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- catechol-O-methyltransferase, COMT gene, gene structure, exon-intron organization, alternative transcription initiation, multiple promoters, proximal promoter, distal promoter, tissue-specific gene expression, membrane-bound COMT, 5' end mapping
- MeSH terms
- Animals, Base Sequence, Catechol O-Methyltransferase, Exons, Humans, Introns, Molecular Sequence Data, Promoter Regions, Genetic, RNA, Messenger, Sequence Homology, Nucleic Acid, Tissue Distribution, Transcription, Genetic, Genomic Library, Sequence Analysis, DNA, Rats
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