Developmental programming of CpG island methylation profiles in the human genome

Publisher Website
Google Scholar
Abstract
A genome-wide analysis of methylated DNA from human embryonic stem cells and adult tissues provides a comprehensive view of unmethylated regions and leads to the identification of sequence motifs that can predict whether a region escapes de novo methylation. This algorithm is used to identify novel, non-CpG unmethylated regions, including intragenic and tissue-specific ones. CpG island–like sequences are commonly thought to provide the sole signals for designating constitutively unmethylated regions in the genome, thus generating open chromatin domains within a sea of global repression. Using a new database obtained from comprehensive microarray analysis, we show that unmethylated regions (UMRs) seem to be formed during early embryogenesis, not as a result of CpG-ness, but rather through the recognition of specific sequence motifs closely associated with transcription start sites. This same system probably brings about the resetting of pluripotency genes during somatic cell reprogramming. The data also reveal a new class of nonpromoter UMRs that become de novo methylated in a tissue-specific manner during development, and this process may be involved in gene regulation. In short, we show that UMRs are an important aspect of genome structure that have a dynamic role in development.