Imprinted control regions include composite DNA elements consisting of the ZFP57 binding site overlapping MLL1...

Mammalian genomes include DNA segments that are imprinted (CpG-methylated) only on one of the two parental chromosomes, leading to parent-of-origin-specific gene expression. The process is regulated by Imprinting Control Regions (ICRs) and germline Differentially Methylated Regions (gDMRs). Previously, ZFP57 was shown to recognize a methylated hexanucleotide in ICRs to maintain allele-specific gene repression. In Bioinformatics analyses, I found that the hexamer occurred frequently in mouse chromosomal DNA, suggesting that beside the ZFP57 binding site (ZFBS), ICRs contained sequence features with unknown characteristics. To identify such features, I examined chromosomal abundance of motifs in which the length of the hexamer was extended by one or several nucleotides. Results led to the discovery of a group of functionally significant composite DNA elements (ZFBS-Morph overlaps) that may play dual roles in the regulation of allele-specific gene expression. Importantly, results of genome-wide evaluations revealed that nearly 90% of the gDMRs included closely-spaced ZFBS-Morph overlaps.