Dynamic changes in the cardiac methylome during postnatal development
Choon Boon Sim, Mark Ziemann, Antony Kaspi, KN Harikrishnan, Jenny Ooi, Ishant Khurana, Lisa Chang, James E Hudson, Assam El-Osta, Enzo R Porrello
FASEB JOURNAL | WILEY | Published : 2015
Relatively little is known about the epigenetic control mechanisms that guide postnatal organ maturation. The goal of this study was to determine whether DNA methylation plays an important role in guiding transcriptional changes during the first 2 wk of mouse heart development, which is an important period for cardiomyocyte maturation, loss of proliferative capacity and loss of regenerative potential. Gene expression profiling (RNA-seq) and genome-wide sequencing of methylated DNA (MBD-seq) identified dynamic changes in the cardiac methylome during postnatal development [2545 differentially methylated regions (DMRs) from P1 to P14 in the mouse]. The vast majority (~80%) of DMRs were hypermet..View full abstract
Awarded by Australian Research Council (ARC) Linkage Infrastructure, Equipment and Facilities Funding (LIEF)
The authors thank Prof. Eric Olson (University of Texas Southwestern Medical Center) for provision of tissue samples and for helpful discussions on the manuscript. The authors thank Ms. Sindhu Igoor (University of Queensland) for technical assistance with animal studies and Mr. Gregory Quaife-Ryan (University of Queensland) for advice on bioinformatics analysis methods. The authors also acknowledge Queensland Facility for Advanced Bioinformatics (QFAB) Bioinformatics and funding provided by Australian Research Council (ARC) Linkage Infrastructure, Equipment and Facilities Funding (LIEF) LE120100071 for providing access to the MetaCore program, as well as support, in part, by the Victorian Government's Operational Infrastructure Support program. E.R.P., A.E.-O., and J.E.H. are supported by fellowships and grants from the National Health and Medical Research Council (Australia) and the National Heart Foundation of Australia. E.R.P. is also supported by a University of Queensland (UQ) postdoctoral fellowship. C.B.S. is supported by a UQ International (UQI) PhD scholarship.