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- Title
Epigenome analyses using BAC microarrays identify evolutionary conservation of tissue-specific methylation of SHANK3.
- Authors
Tsui-Ting Ching; Maunakea, Alika K.; Jun, Peter; Hong, Chibo; Zardo, Giuseppe; Pinkel, Daniel; Albertson, Donna G.; Fridlyand, Jane; Jian-Hua Mao; Shchors, Ksenya; Weiss, William A.; Costello, Joseph F.
- 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.
- Publication
Nature Genetics, 2005, Vol 37, Issue 6, p645
- ISSN
1061-4036
- Publication type
Academic Journal
- DOI
10.1038/ng1563