Dynamic changes in the cardiac methylome during postnatal development.

Sim, Choon Boon, Ziemann, Mark, Kaspi, Antony, Harikrishnan, K. N., Ooi, Jenny, Khurana, Ishant, Chang, Lisa, Hudson, James E., El-Osta, Assam and Porrello, Enzo R. (2015) Dynamic changes in the cardiac methylome during postnatal development.. Faseb Journal, 4 4: 1329-1343. doi:10.1096/fj.14-264093

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Author Sim, Choon Boon
Ziemann, Mark
Kaspi, Antony
Harikrishnan, K. N.
Ooi, Jenny
Khurana, Ishant
Chang, Lisa
Hudson, James E.
El-Osta, Assam
Porrello, Enzo R.
Title Dynamic changes in the cardiac methylome during postnatal development.
Journal name Faseb Journal   Check publisher's open access policy
ISSN 0892-6638
Publication date 2015-04-01
Year available 2014
Sub-type Article (original research)
DOI 10.1096/fj.14-264093
Volume 4
Issue 4
Start page 1329
End page 1343
Total pages 15
Place of publication Bethesda, MD,United States
Publisher Federation of American Societies for Experimental Biology
Language eng
Formatted abstract
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 hypermethylated between P1 and P14, and these hypermethylated regions were associated with transcriptional shut down of important developmental signaling pathways, including Hedgehog, bone morphogenetic protein, TGF-β, fibroblast growth factor, and Wnt/β-catenin signaling. Postnatal inhibition of DNA methylation with 5-aza-2'-deoxycytidine induced a marked increase (~3-fold) in cardiomyocyte proliferation and ~50% reduction in the percentage of binucleated cardiomyocytes compared with saline-treated controls. This study provides novel evidence for widespread alterations in DNA methylation during postnatal heart maturation and suggests that cardiomyocyte cell cycle arrest during the neonatal period is subject to regulation by DNA methylation.
Keyword Binucleation
Cardiomyocyte proliferation
Neonatal heart
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID LE120100071
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
School of Biomedical Sciences Publications
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Citation counts: TR Web of Science Citation Count  Cited 15 times in Thomson Reuters Web of Science Article | Citations
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Created: Wed, 28 Jan 2015, 18:25:21 EST by Enzo Porrello on behalf of School of Biomedical Sciences