DNA methylation regulates tissue‐specific expression of Shank3
Abstract
Tissue‐specific gene expression can be controlled by epigenetic modifications such as DNA methylation. SHANK3 , together with its homologues SHANK1 and SHANK2 , has a central functional and structural role in excitatory synapses and is involved in the human chromosome 22q13 deletion syndrome. In this report, we show by DNA methylation analysis in lymphocytes, brain cortex, cerebellum and heart that the three SHANK genes possess several methylated CpG boxes, but only SHANK3 CpG islands are highly methylated in tissues where protein expression is low or absent and unmethylated where expression is present. SHANK3 protein expression is significantly reduced in hippocampal neurons after treatment with methionine, while HeLa cells become able to express SHANK3 after treatment with 5‐Aza‐2′‐deoxycytidine. Altogether, these data suggest the existence of a specific epigenetic control mechanism regulating SHANK3 , but not SHANK1 and SHANK2 , expression.
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SHANK3 expression in brain and other tissues is regulated by DNA methylation.
“SHANK3 expression in brain and other tissues is regulated by DNA methylation [ 161 , 162 ], and increased levels of SHANK3 DNA methylation, corresponding to decreased isoform-specific expression of SHANK3, have been observed in postmortem brain tissues of ASD patients compared with neurotypical control tissues [ 162 ].”
From DNA methylation: a mechanism linking environmental chemical exposures to risk of autism spectrum disorders? (2016) · cites this paper as [161]
DNA methylation and histone deacetylase inhibitors modulate isoform-specific Shank3 expression in cultured neurons.
“Both DNA methylation and histone deacetylase inhibitors have been shown to modulate the isoform specific gene expression of Shank3 in cultured neurons (Beri et al., 2007; Maunakea et al., 2010).”
From Modeling Autism by SHANK Gene Mutations in Mice (2013) · cites this paper as Beri et al., 2007
SHANK3 has five CpG islands across the gene, and these islands display brain-specific and cell type-specific DNA methylation.
“To add further complexity, SHANK3 has five CpG islands across the gene and these CpG islands display brain-specific and cell type-specific DNA methylation (Figure 1A) (Beri et al., 2007; Ching et al., 2005; Maunakea et al., 2010).”
From Modeling Autism by SHANK Gene Mutations in Mice (2013) · cites this paper as Beri et al., 2007
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- Authors
- Beri, S., Tonna, N., Menozzi, G., Bonaglia, M. C., Sala, C., & Giorda, R.
- Affiliations
- IRCCS Eugenio Medea (IT)
- University of Milan (IT)
- Venue
- Journal of Neurochemistry
- Publisher
- Wiley
- Published
- 2007-02-28
- Volume
- 101
- Issue
- 5
- Pages
- 1380-1391
- ISSN
- 0022-3042 (ISSN-L)
- 1471-4159
- OpenAlex
- W2038894983
- Cited by
- 74
- References
- 50
- Citations by year
- 2026: 2 · 2025: 3 · 2024: 4 · 2023: 2 · 2022: 1 · 2021: 3 · 2020: 4 · 2019: 3 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 8 · 2014: 6 · 2013: 9 · 2012: 6
- FWCI
- 0.66
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neurochemistry (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Keywords
- DNA methylation, SHANK3, Shank1, Shank2, tissue-specific gene expression, CpG islands, epigenetic regulation, excitatory synapses, hippocampal neurons, methionine, decitabine, demethylation, cerebral cortex, cerebellum, heart, lymphocytes
- MeSH terms
- Decitabine, Animals, Azacitidine, Brain, Carrier Proteins, Cells, Cultured, Embryo, Mammalian, Enzyme Inhibitors, Gene Expression Regulation, Heart, Hippocampus, Humans, Lymphocytes, Methionine, Microfilament Proteins, Nerve Tissue Proteins, Neurons, Tissue Distribution, Transfection, Gene Expression, Gene Expression Regulation, Neoplastic, CpG Islands, DNA Methylation, RNA, Small Interfering, Green Fluorescent Proteins, Rats
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