Dynamic Mouse Epigenome
Dynamic epigenomic oscillations in differentiated cells
Dynamic gene expression patterns in adult organs are necessary for adaptation to changing environments. Large numbers of transcripts show daily high-amplitude ~24-hour oscillations in various mouse organs including the liver (PMID: 12152080, PMID: 17298173). Loss of these transcriptional oscillations reduces the organism’s fitness and increases susceptibility to chronic diseases and cancer (ref). While variations in the local chromatin environment underlie transcriptional changes during cellular differentiation and transformation, whether comparable changes in the epigenome underlie dynamic transcription in normal differentiated adult organs has not been investigated genome-wide. We used deep-sequencing methods to monitor strand-specific RNA transcripts, DNA methylation and various histone modifications in the adult mouse liver throughout a 24-hour period. We found that the chromatin environment of genes undergoing oscillating RNA expression is dynamic, while DNA methylation in their promoters remains stable.  All histone modifications tested showed oscillations at hundreds of loci with varying amplitude, phase and temporal relation with the accompanying transcript oscillations. We also found oscillating coding and non-coding natural antisense transcripts, offering potential new mechanisms for dynamic control of gene expression. Our results suggest that the epigenome is highly dynamic, and that transient changes in local chromatin environments are independent of a single specific transcription factor.
Dynamic gene expression patterns in adult organs are necessary for adaptation to changing environments. Large numbers of transcripts show daily high-amplitude ~24-hour oscillations in various mouse organs including the liver (PMID: 12152080, PMID: 17298173). Loss of these transcriptional oscillations reduces the organism’s fitness and increases susceptibility to chronic diseases and cancer (ref). While variations in the local chromatin environment underlie transcriptional changes during cellular differentiation and transformation, whether comparable changes in the epigenome underlie dynamic transcription in normal differentiated adult organs has not been investigated genome-wide. We used deep-sequencing methods to monitor strand-specific RNA transcripts, DNA methylation and various histone modifications in the adult mouse liver throughout a 24-hour period. We found that the chromatin environment of genes undergoing oscillating RNA expression is dynamic, while DNA methylation in their promoters remains stable.  All histone modifications tested showed oscillations at hundreds of loci with varying amplitude, phase and temporal relation with the accompanying transcript oscillations. We also found oscillating coding and non-coding natural antisense transcripts, offering potential new mechanisms for dynamic control of gene expression. Our results suggest that the epigenome is highly dynamic, and that transient changes in local chromatin environments are independent of a single specific transcription factor.