The present invention provides compositions and methods for selectively enriching genomic CpG island (CGI)- and other epigenetically informative CG-rich polynucleotide targets. The method involves co-incubation of denatured or partially denatured polynucleotide fragments containing the CGI- or CG-targeted region(s) of interest with an oligonucleotide capture pool collectively designed to selectively target CGIs. The oligonucleotide capture pool includes a plurality of different oligonucleotides, each oligonucleotide coupled to a capture tag, whereby the oligonucleotide includes a CpG target sequence restricted to 4 to 10 bases. Upon binding, capture oligonucleotides bound to the target fragments are enriched by separating the bound fragments from the unbound fragments. The enriched fragments may be subjected to further analyses, including bisulfite sequencing to generate a methylation profile at the single nucleotide level.