Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3
Abstract
CpG islands are present in one-half of all human and mouse genes and typically overlap with promoters or exons. We developed a method for high-resolution analysis of the methylation status of CpG islands genome-wide, using arrays of BAC clones and the methylation-sensitive restriction enzyme NotI. Here we demonstrate the accuracy and specificity of the method. By computationally mapping all NotI sites, methylation events can be defined with single-nucleotide precision throughout the genome. We also demonstrate the unique expandability of the array method using a different methylation-sensitive restriction enzyme, BssHII. We identified and validated new CpG island loci that are methylated in a tissue-specific manner in normal human tissues. The methylation status of the CpG islands is associated with gene expression for several genes, including SHANK3, which encodes a structural protein in neuronal postsynaptic densities. Defects in SHANK3 seem to underlie human 22q13 deletion syndrome. Furthermore, these patterns for SHANK3 are conserved in mice and rats.
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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 Ching et al., 2005
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- Authors
- Ching, T.-T., Maunakea, A. K., Jun, P., Hong, C., Zardo, G., Pinkel, D., Albertson, D. G., Fridlyand, J., Mao, J.-H., Shchors, K., Weiss, W. A., & Costello, J. F.
- Affiliations
- University of California, San Francisco (US)
- Corresponding author
- Costello, Joseph F
- ORCID
- Venue
- Nature Genetics
- Published
- 2005-05-15
- Volume
- 37
- Issue
- 6
- Pages
- 645-651
- ISSN
- 1061-4036 (ISSN-L)
- 1546-1718
- OpenAlex
- W1979863914
- Cited by
- 159
- References
- 45
- Citations by year
- 2025: 1 · 2024: 2 · 2023: 6 · 2022: 1 · 2021: 5 · 2020: 4 · 2018: 2 · 2017: 4 · 2016: 6 · 2015: 7 · 2014: 5 · 2013: 6 · 2012: 11
- FWCI
- 8.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Licence
- www.springer.com/tdm (tdm)
- Locations
- Nature Genetics (publishedVersion)
- PubMed (publishedVersion)
- IRIS Research product catalog (Sapienza University of Rome) (submittedVersion)
- Funders
- National Institutes of Health
- University of California, San Francisco
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
- Keywords
- DNA methylation, CpG islands, tissue-specific methylation, SHANK3, 22q13 deletion syndrome, gene expression, epigenome, evolutionary conservation
- MeSH terms
- Animals, Carrier Proteins, Humans, Nerve Tissue Proteins, Organ Specificity, Regulatory Sequences, Nucleic Acid, Deoxyribonucleases, Type II Site-Specific, Conserved Sequence, CpG Islands, DNA Methylation, Reverse Transcriptase Polymerase Chain Reaction, Oligonucleotide Array Sequence Analysis, Chromosomes, Artificial, Bacterial, Mice
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