Pluto Bioinformatics

GSE46953: Default DNA Methylation is Preceded by Broad, Low-Level Transcription in Fetal Male Germ Cells and Is Inversely Patterned by Dynamic H3K4 Methylation (RNA-Seq)

Bulk RNA sequencing

To understand what dictates the emerging patterns of de novo DNA methylation, we mapped DNA methylation, chromatin, and transcription changes in purified fetal mouse germ cells using MIRA-chip, ChIP-chip, and strand-specific RNA-seq, respectively. De novo methylation occurred without any apparent trigger from preexisting repressing chromatin marks but was preceded by broad, low-level transcription along the entire genome in prospermatogonia. Only distinct short sequences remained unmethylated, precisely aligned with constitutive or emerging peaks of H3K4me2. Establishment of methylation at differentially methylated regions (DMRs) of imprinted genes, CpG islands, and IAPs followed these same default rules. Transcription run-through occurred at paternal DMRs with no- or diminishing H3K4me2 peaks. Maternal DMRs remained unmethylated among highly methylated DNA at precisely aligned H3K4me2 peaks with transcription initiating at least in one strand. Our results suggest that the pattern of de novo DNA methylation in prospermatogonia is dictated by opposing actions of broad, low-level transcription and dynamic patterns of active chromatin. SOURCE: Xiwei Wu (xwu@coh.org) - City of Hope National Medical Center