title: Changes in gene methylation patterns in neonatal murine hearts: Implications for the regenerative potential.
abstract: BACKGROUND
  The neonatal murine heart is able to regenerate after severe injury; this capacity however, quickly diminishes and it is lost within the first week of life. DNA methylation is an epigenetic mechanism which plays a crucial role in development and gene expression regulation. Under investigation here are the changes in DNA methylation and gene expression patterns which accompany the loss of regenerative potential.
  
  
  RESULTS
  The MeDIP-chip (methylated DNA immunoprecipitation microarray) approach was used in order to compare global DNA methylation profiles in whole murine hearts at day 1, 7, 14 and 56 complemented with microarray transcriptome profiling. We found that the methylome transition from day 1 to day 7 is characterized by the excess of genomic regions which gain over those that lose DNA methylation. A number of these changes were retained until adulthood. The promoter genomic regions exhibiting increased DNA methylation at day 7 as compared to day 1 are significantly enriched in the genes critical for heart maturation and muscle development. Also, the promoter genomic regions showing an increase in DNA methylation at day 7 relative to day 1 are significantly enriched with a number of transcription factors binding motifs including those of Mfsd6l, Mef2c, Meis3, Tead4, and Runx1.
  
  
  CONCLUSIONS
  The results indicate that the extensive alterations in DNA methylation patterns along the development of neonatal murine hearts are likely to contribute to the decline of regenerative capabilities observed shortly after birth. This conclusion is supported by the evidence that an increase in DNA methylation in the neonatal murine heart from day 1 to day 7 occurs in the promoter regions of genes playing important roles in cardiovascular system development.
authors.affiliation: Department of Molecular Biotechnology and Microbiology, Gdańsk University of Technology, Gdańsk, Poland.
authors.forename: Bartosz
authors.initials: B
authors.lastname: Górnikiewicz
authors.affiliation: Department of Biology and Pharmaceutical Botany, Medical University of Gdańsk, Gdańsk, Poland.
authors.forename: Anna
authors.initials: A
authors.lastname: Ronowicz
authors.affiliation: Department of Probability and Biomathematics, Gdańsk University of Technology, Gdańsk, Poland.
authors.forename: Michał
authors.initials: M
authors.lastname: Krzemiński
authors.affiliation: Department of Molecular Biotechnology and Microbiology, Gdańsk University of Technology, Gdańsk, Poland. psach@pg.gda.pl.
authors.forename: Paweł
authors.initials: P
authors.lastname: Sachadyn
mesh_terms: D000818:Animals; D000831:Animals, Newborn; D018899:CpG Islands; D019175:DNA Methylation; D044127:Epigenesis, Genetic; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental; D006321:Heart / Q000502:physiology*; D047468:Immunoprecipitation; D051379:Mice; D008810:Mice, Inbred C57BL; D020411:Oligonucleotide Array Sequence Analysis; D011401:Promoter Regions, Genetic; D012038:Regeneration / Q000235:genetics*
keywords: Heart; Methylome; Microarray profiling; Neonatal mouse; Regeneration; Transcription factors; Transcriptome