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Cited by 4Neurotransmitter Receptor Influence on BehaviorGenetic Associations and EpidemiologyRNA Research and Splicing

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Effects of HTR1B 3′ region polymorphisms and functional regions on gene expression regulation

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Xia, Xi, Ding, Mei, Xuan, Jin-feng, Xing, Jia-xin, Pang, Hao, Yao, Jun, Wu, Xue, Wang, Bao-jie·2020·BMC Genetics
DOI 10.1186/s12863-020-00886-8PMC PMC7372893

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Abstract

Background: The HTR1B gene encodes the 5-hydroxytryptamine (5-HT1B) receptor, which is involved in a variety of brain activities and mental disorders. The regulatory effects of non-coding regions on genomic DNA are one of many reasons for the cause of genetic-related diseases. Post-transcriptional regulation that depends on the function of 3′ regulatory regions plays a particularly important role. This study investigated the effects, on reporter gene expression, of several haplotypes of the HTR1B gene (rs6297, rs3827804, rs140792648, rs9361234, rs76194807, rs58138557, and rs13212041) and truncated fragments in order to analyze the function of the 3′ region of HTR1B . Results: We found that the haplotype, A-G-Del-C-T-Ins-A, enhanced the expression level compared to the main haplotype; A-G-Del-C-G-Ins-A; G-G-Del-C-G-Ins-G decreased the expression level. Two alleles, rs76194807T and rs6297G, exhibited different relative luciferase intensities compared to their counterparts at each locus. We also found that + 2440 ~ + 2769 bp and + 1953 ~ + 2311 bp regions both had negative effects on gene expression. Conclusions: The 3′ region of HTR1B has a regulatory effect on gene expression, which is likely closely associated with the interpretation of HTR1B -related disorders. In addition, the HTR1B 3′ region includes several effector binding sites that induce an inhibitory effect on gene expression.

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Fig. 1 Relative fluorescence intensities of haplotype recombinants in SK-N-SH and HEK-293 cells. The haplotypes, from H2 to H7, were compared with the major haplotype, H1; the H2 haplotype was compared to the H3 haplotype. The H4 haplotype showed a higher relative fluorescence intensity than that of the HI haplotype in SK-N-SH cells. The relative fluorescence intensity of the H3 haplotype was lower than that of H1and H2 haplotypes in HEK-293 cells
Fig. 1 Relative fluorescence intensities of haplotype recombinants in SK-N-SH and HEK-293 cells. The haplotypes, from H2 to H7, were compared with the major haplotype, H1; the H2 haplotype was compared to the H3 haplotype. The H4 haplotype showed a higher relative fluorescence intensity than that of the HI haplotype in SK-N-SH cells. The relative fluorescence intensity of the H3 haplotype was lower than that of H1and H2 haplotypes in HEK-293 cellsCC BY · PubMed Central
Fig. 2 Relative fluorescence intensities of the truncated sequence recombinants in SK-N-SH, HEK-293, and U87 cells. Two regions, (+ 1754 to + 2769) versus (+ 1754 to + 2440), and (+ 1754 to + 2311) versus (+ 1754 to + 1953), showed significant regulatory effects on gene expression between in all three cell lines. Relative fluorescence intensity is expressed as the mean ± standard deviation (SD). The no-insert pmirGLO vector (pmirGLO basic) is a control plasmid
Fig. 2 Relative fluorescence intensities of the truncated sequence recombinants in SK-N-SH, HEK-293, and U87 cells. Two regions, (+ 1754 to + 2769) versus (+ 1754 to + 2440), and (+ 1754 to + 2311) versus (+ 1754 to + 1953), showed significant regulatory effects on gene expression between in all three cell lines. Relative fluorescence intensity is expressed as the mean ± standard deviation (SD). The no-insert pmirGLO vector (pmirGLO basic) is a control plasmidCC BY · PubMed Central
Fig. 3 Truncated sequence recombinants in the 3′ regulatory region of HTR1B. The target gene was obtained using the GenBank reference sequence NC_000006.12 (Homo sapiens chromosome 6, GRCh38.p7 Primary Assembly). The DNA fragments shared a common 5′ end at + 1754 bp (TSS, + 1)
Fig. 3 Truncated sequence recombinants in the 3′ regulatory region of HTR1B. The target gene was obtained using the GenBank reference sequence NC_000006.12 (Homo sapiens chromosome 6, GRCh38.p7 Primary Assembly). The DNA fragments shared a common 5′ end at + 1754 bp (TSS, + 1)CC BY · PubMed Central

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Citations

Cites

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Metadata

Authors
Xia, X., Ding, M., Xuan, J.-F., Xing, J.-X., Pang, H., Yao, J., Wu, X., & Wang, B.-J.
Affiliations
China Medical University (CN)
ORCID
Venue
BMC Genetics
Publisher
Springer Science and Business Media LLC
Published
2020-07-20
Volume
21
Issue
1
Pages
79-79
ISSN
1471-2156 (ISSN-L)
DOI
10.1186/s12863-020-00886-8
PMC
PMC7372893
OpenAlex
W3045354361
Cited by
4
References
2
Citations by year
2026: 1 · 2025: 1 · 2024: 1 · 2022: 1
FWCI
0.11
Type
journal article
Language
en
Open access
Licence
Locations
  • BMC Genetics (publishedVersion, cc-by)
  • Research Square (acceptedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
  • DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
Funders
China Medical University
Topics
  • Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › RNA Research and Splicing
Keywords
5-HT1B receptor, 3' untranslated region, genetic polymorphism, haplotypes, post-transcriptional regulation, gene expression regulation, transcriptional repression, binding sites, reporter gene expression
MeSH terms
Alleles, Cell Line, Gene Expression Regulation, Haplotypes, Humans, Polymorphism, Genetic, MicroRNAs, Receptor, Serotonin, 5-HT1B

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