Rapid, sensitive, reproducible high-throughput methods for detecting methylation patterns in samples of nucleic acid, especially in the promoter region of genes which are enriched with CpG islands, are provided. The methods include isolating complexes of methylated DNA and methylation binding protein, optionally amplifying the isolated methylated DNA, and detecting the methylated DNA or its amplification products in a multiplex and robust manner. By using the inventive methodology, methylated and unmethylated sequences present in the original sample of nucleic acid can be distinguished. By profiling and comparing the methylation status of genes in different samples, one can utilize the information for diagnosis and treatment of diseases or conditions associated with aberrant DNA hypermethylation or hypomethylation.