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Gender-specific postnatal demethylation and establishment of epigenetic memory.

ABSTRACT: DNA methylation patterns are set up in a relatively fixed programmed manner during normal embryonic development and are then stably maintained. Using genome-wide analysis, we discovered a postnatal pathway involving gender-specific demethylation that occurs exclusively in the male liver. This demodification is programmed to take place at tissue-specific enhancer sequences, and our data show that the methylation state at these loci is associated with and appears to play a role in the transcriptional regulation of nearby genes. This process is mediated by the secretion of testosterone at the time of sexual maturity, but the resulting methylation profile is stable and therefore can serve as an epigenetic memory even in the absence of this inducer. These findings add a new dimension to our understanding of the role of DNA methylation in vivo and provide the foundations for deciphering how environment can impact on the epigenetic regulation of genes in general.

SUBMITTER: Reizel Y

PROVIDER: S-EPMC4421981 | biostudies-literature | 2015 May

REPOSITORIES: biostudies-literature

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Gender-specific post-natal demethylation and establishment of epigenetic memory

Project description:DNA methylation patterns are set up in a relatively fixed programmed manner during normal embryonic development and are then stably maintained. Using genome-wide analysis, we have discovered a postnatal pathway involving gender-specific demethylation that occurs exclusively in the male liver. This demodification is programmed to take place at tissue-specific enhancer sequences, and our data show that the methylation state at these loci is associated with and appears to play a role in the transcriptional regulation of nearby genes. This process is mediated by the secretion of testosterone at the time of sexual maturity, but the resulting methylation profile is stable and therefore can serve as an epigenetic memory even in the absence of this inducer. These findings add a new dimension to our understanding of the role of DNA methylation in vivo and provide the foundations for deciphering how environment can impact on the epigenetic regulation of genes, in general. DNA methylation profile of male and female mouse and Human tissues was generated using the RRBS protocol followed by deep sequncing. Whole genome DNA methylation profile using deep sequencing was genereted for male and female mouse tissues. RNAseq was performed on male and female mouse tissues.

2015-05-03 | E-GEOD-60012 | biostudies-arrayexpress

Gender-specific post-natal demethylation and establishment of epigenetic memory

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Gender-specific post-natal demethylation and establishment of epigenetic memory

Project description:Gender-specific post-natal demethylation and establishment of epigenetic memory

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FoxA-dependent demethylation of DNA initiates epigenetic memory of cellular identity.

Project description:Tissue-specific DNA methylation patterns are created by transcription factors that recruit methylation and demethylation enzymes to cis-regulatory elements. To date, it is not known whether transcription factors are needed to continuously maintain methylation profiles in development and mature tissues or whether they only establish these marks during organ development. We queried the role of the pioneer factor FoxA in generating hypomethylated DNA at liver enhancers. We discovered a set of FoxA-binding sites that undergo regional, FoxA-dependent demethylation during organ development. Conditional ablation of FoxA genes in the adult liver demonstrated that continued FoxA presence was not required to maintain the hypomethylated state, even when massive cell proliferation was induced. This study provides strong evidence for the stable, epigenetic nature of tissue-specific DNA methylation patterns directed by lineage-determining transcription factors during organ development.

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