This study presents a comprehensive map of cis-regulatory sequences in the mouse genome, identifying nearly 300,000 non-redundant cis-regulatory elements, including promoters, enhancers, and CTCF-binding sites. The authors used ChIP-Seq to analyze chromatin marks and transcription factors in 19 tissues and cell types, revealing that these elements account for 11% of the mouse genome. The identified elements show high sequence conservation, particularly in promoters, and are associated with tissue-specific gene expression. The study also highlights the tissue-specific occupancy of enhancers and promoters, with enhancers being more tissue-specific than promoters. Additionally, the authors developed an algorithm to define enhancer-promoter units (EPUs), which help in associating enhancers with their target genes. The EPUs are correlated with topological domains defined by chromatin interactions, suggesting a link between physical and functional genome organization. The findings provide valuable resources for understanding mammalian genome regulation and tissue-specific gene expression.This study presents a comprehensive map of cis-regulatory sequences in the mouse genome, identifying nearly 300,000 non-redundant cis-regulatory elements, including promoters, enhancers, and CTCF-binding sites. The authors used ChIP-Seq to analyze chromatin marks and transcription factors in 19 tissues and cell types, revealing that these elements account for 11% of the mouse genome. The identified elements show high sequence conservation, particularly in promoters, and are associated with tissue-specific gene expression. The study also highlights the tissue-specific occupancy of enhancers and promoters, with enhancers being more tissue-specific than promoters. Additionally, the authors developed an algorithm to define enhancer-promoter units (EPUs), which help in associating enhancers with their target genes. The EPUs are correlated with topological domains defined by chromatin interactions, suggesting a link between physical and functional genome organization. The findings provide valuable resources for understanding mammalian genome regulation and tissue-specific gene expression.