A draft map of cis-regulatory sequences in the mouse genome

The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 billion bases of the mouse genome share a high degree of conservation with the human genome, so a thorough annotation of the mouse genome will be of significant value to understanding the function of the human genome. To date, most of the functional sequences in the mouse genome have yet to be found, and the cis-regulatory sequences in particular are still poorly annotated. Comparative genomics has been a powerful tool for the discovery of these sequences, but it alone cannot resolve their temporal and spatial functions. Recently, ChIP-Seq has been developed to identify cis-regulatory elements in the genomes of several organisms including human, D. melanogaster and C. elegans. We have applied the same experimental approach to a diverse set of 19 tissues and cell types in the mouse, producing a map of nearly 300,000 murine cis-regulatory sequences. This map provides functional annotation to nearly 11% of the mouse genome, and over 70% of conserved, non-coding sequences (CNS). We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we demonstrate that much of the mouse genome is organized into domains of coordinately regulated enhancers and promoters. Our results provide a resource for the annotation of functional elements in the mammalian genome and study of mechanisms regulating tissue-specific gene expression. This SuperSeries is composed of the SubSeries listed below.