Novel imprints in mouse blastocysts are predominantly DNA methylation independent

Autor: Martin Leeb, Simon Hippenmeyer, Florian M. Pauler, Matthias Farlik, Perry Acf, Maki Asami, Ernest D. Laue, Toru Suzuki, Laura Santini, Florian Halbritter, Nick Warr, Xiaoyan Ma, Julia Ramesmayer, Andreas Beyer, Fabian Titz-Teixeira, Andreas Lackner, Christoph Bock
Rok vydání: 2020
Předmět:
Popis: In mammals, chromatin marks at imprinted genes are asymmetrically inherited to control parentally-biased gene expression. This control is thought predominantly to involve parent-specific differentially methylated regions (DMR) in genomic DNA. However, neither parent-of-origin-specific transcription nor DMRs have been comprehensively mapped. We here address this by integrating transcriptomic and epigenomic approaches in mouse preimplantation embryos (blastocysts). Transcriptome-analysis identified 71 genes expressed with previously unknown parent-of-origin-specific expression in blastocysts (nBiX: novel blastocyst-imprinted expression). Uniparental expression of nBiX genes disappeared soon after implantation. Micro-whole-genome bisulfite sequencing (μWGBS) of individual uniparental blastocysts detected 859 DMRs. Only 18% of nBiXs were associated with a DMR, whereas 60% were associated with parentally-biased H3K27me3. This suggests a major role for Polycomb-mediated imprinting in blastocysts. Five nBiX-clusters contained at least one known imprinted gene, and five novel clusters contained exclusively nBiX-genes. These data suggest a complex program of stage-specific imprinting involving different tiers of regulation.
Databáze: OpenAIRE