The Mouse ENCODE Consortium has mapped various aspects of the mouse genome, including transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications, and replication domains, across diverse cell and tissue types. By comparing these data with the human genome, the consortium has confirmed substantial conservation in annotated potential functional sequences while also identifying significant divergence in sequences involved in transcriptional regulation, chromatin state, and higher-order chromatin organization. This study provides a comprehensive resource for understanding mammalian biology and mechanisms of human diseases, highlighting both conserved and divergent features between the mouse and human genomes. Key findings include: - **Conservation and Divergence**: While much of the genome is conserved, many mouse genes involved in distinct biological pathways show significant divergence from their human orthologues. - **Transcriptional Activities**: The mouse genome is pervasively transcribed, with 46% capable of producing polyadenylated transcripts. - **Cis-Regulatory Elements**: The consortium identified a large number of cis-regulatory elements, including promoters and enhancers, using methods such as DNase I hypersensitivity mapping, ChIP-seq, and histone modification analysis. - **Gene Expression Patterns**: Gene expression patterns tend to cluster more by species than by tissue, with some genes showing more tissue-specific variation and others showing more species-specific variation. - **Chromatin States**: Chromatin states, such as active and repressed states, are stable within individual cell lineages and reflect tissue and cell identities. - **Replication Timing**: Replication timing boundaries are conserved between mouse and human, with developmental plasticity observed during differentiation. - **Species-Specific Regulatory Sequences**: A significant fraction of regulatory sequences are species-specific, particularly near genes involved in immune function, suggesting rapid evolution of regulatory mechanisms. Overall, the study provides a detailed catalog of potential functional elements in the mouse genome, offering valuable insights into the evolutionary forces acting on genes and their regulatory regions.The Mouse ENCODE Consortium has mapped various aspects of the mouse genome, including transcription, DNase I hypersensitivity, transcription factor binding, chromatin modifications, and replication domains, across diverse cell and tissue types. By comparing these data with the human genome, the consortium has confirmed substantial conservation in annotated potential functional sequences while also identifying significant divergence in sequences involved in transcriptional regulation, chromatin state, and higher-order chromatin organization. This study provides a comprehensive resource for understanding mammalian biology and mechanisms of human diseases, highlighting both conserved and divergent features between the mouse and human genomes. Key findings include: - **Conservation and Divergence**: While much of the genome is conserved, many mouse genes involved in distinct biological pathways show significant divergence from their human orthologues. - **Transcriptional Activities**: The mouse genome is pervasively transcribed, with 46% capable of producing polyadenylated transcripts. - **Cis-Regulatory Elements**: The consortium identified a large number of cis-regulatory elements, including promoters and enhancers, using methods such as DNase I hypersensitivity mapping, ChIP-seq, and histone modification analysis. - **Gene Expression Patterns**: Gene expression patterns tend to cluster more by species than by tissue, with some genes showing more tissue-specific variation and others showing more species-specific variation. - **Chromatin States**: Chromatin states, such as active and repressed states, are stable within individual cell lineages and reflect tissue and cell identities. - **Replication Timing**: Replication timing boundaries are conserved between mouse and human, with developmental plasticity observed during differentiation. - **Species-Specific Regulatory Sequences**: A significant fraction of regulatory sequences are species-specific, particularly near genes involved in immune function, suggesting rapid evolution of regulatory mechanisms. Overall, the study provides a detailed catalog of potential functional elements in the mouse genome, offering valuable insights into the evolutionary forces acting on genes and their regulatory regions.