Abstract
The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. Phase III of the ENCODE Project profiled 66 mouse epigenomes across twelve tissues at daily intervals from embryonic day 11.5 to birth. Applying the ChromHMM algorithm to these epigenomes, we annotated eighteen chromatin states with characteristics of promoters, enhancers, transcribed regions, repressed regions, and quiescent regions. Our integrative analyses delineate the tissue specificity and developmental trajectory of the loci in these chromatin states. Approximately 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me3. Highly evolutionarily conserved, these loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes. This collection of chromatin state assignments provides a useful resource for studying mammalian development.
Highlights
The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs
We named our chromatin states to maximize consistency with earlier ChromHMM publications[6,10,34]; two are proximal to active TSSs (Tss and TssFlnk, on average occupying 1.4% of the mouse genome); two states associate with actively transcribed genes (Tx and TxWk, 7.2%); five states are enhancer-related (Enh, EnhLo, EnhPois, EnhPr, and EnhG; 3.9%); one bivalent state often falls near inactive TSSs (TssBiv, 0.3%); three states are repressive (ReprPC and ReprPCWk enriched in H3K27me3, 3.7%; and Het in H3K9me3, 1.8%); and five states are quiescent (QuiesG, quiescent state (Quies), Quies[2], Quies[3], and Quies4; 78.7%)
We recapitulated the human states previously defined by the Roadmap Epigenomics Consortium[10] and refined enhancer, bivalent, and quiescent states
Summary
The morphologically and functionally distinct cell types of a multicellular organism are maintained by their unique epigenomes and gene expression programs. 0.3% of each epigenome is assigned to a bivalent chromatin state, which harbors both active marks and the repressive mark H3K27me[3] Evolutionarily conserved, these loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes. These loci are enriched in silencers bound by polycomb repressive complex proteins, and the transcription start sites of their silenced target genes This collection of chromatin state assignments provides a useful resource for studying mammalian development. 1234567890():,; Multicellular organisms maintain myriad cell types along distinct lineages to carry out cellular programs required for development and survival These cell types have the same genome but different epigenomes, characterized by chromatin accessibility, histone modifications, and DNA methylation, which cooperate with trans-factors to regulate gene expression and downstream activities. All 66 epigenomes were accompanied by transcriptome sequencing (RNA-seq)[21] and DNase-seq, another technique for measuring chromatin accessibility[22]
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