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

By Yin Shen, Feng Yue, David F. McCleary, Z. Ye, Lee E. Edsall, Samantha Kuan, Ulrich Wagner, J. Dixon, Leonard K. Lee, Victor V Lobanenkov and 1 more. Nature, 2012

1,404 citations recorded by the source corpus.

The laboratory mouse is the most widely used mammalian model organism in biomedical research. The 2.6 × 109 bases of the mouse genome possess 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. So far, 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 on its own it 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 humans, Drosophila melanogaster and Caenorhabditis elegans. Here we apply the same experimental approach to a diverse set of 19 tissues and cell types in the mouse to produce a map of nearly 300,000 murine cis-regulatory sequences. The annotated sequences add up to 11% of the mouse genome, and include more than 70% of conserved non-coding sequences. We define tissue-specific enhancers and identify potential transcription factors regulating gene expression in each tissue or cell type. Finally, we show 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 for the study of mechanisms regulating tissue-specific gene expression.

Subfields: Molecular Biology, Plant Science

View Paper: https://www.semanticscholar.org/paper/b0fb4a8f6a83a2dc802fd9d4d0ac8afce361d8e3

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Citations in the corpus

Exploring the three-dimensional organization of genomes: interpreting chromatin interaction data (2013, background): “Computational predictions based on correlations between gene activity and activity of distal elements across panels of cell lines also led to the prediction that genes are regulated by multiple distal elements 54–56 .”
Targeted degradation of CTCF decouples local insulation of chromosome domains from genomic compartmentalization (2017, neutral): “(10%) connect to an active regulatory region before treatment, based on H3K27Ac enrichment (Shen et al., 2012).”
Super-enhancers in the control of cell identity and disease. (2013, neutral): “The set of enhancers that control any one cell’s gene expression program is probably best defined in murine embryonic stem cells (ESCs).”
Control of cell identity genes occurs in insulated neighborhoods in mammalian chromosomes (2014, positive): “Prior studies have suggested there can be more frequent interactions between enhancers and genes (Kieffer-Kwon et al., 2013; Sanyal et al., 2012; Shen et al., 2012); our high-confidence data is not saturating and does not address the upper limits of these interactions (Figure S1H, Extended Experimen”
Topological Domains in Mammalian Genomes Identified by Analysis of Chromatin Interactions (2012, background): “H3K4me3, H3K4me1, H3K27ac, p300, CTCF, ChIPseq, mESC and cortex RNA-seq Figures 1-4, Supplemental Figures 5,10,2023 Shen, Y. et al. A Map of cis-Regulatory Sequences in the Mouse Genome. in submission (2012).(32) Lung Fibroblast 5C Supplemental Figure 4 Wang, K.C. et al. A long noncoding RNA maintai”
TopDom: an efficient and deterministic method for identifying topological domains in genomes (2015, methodology): “For mouse cortex and mESC cells, we collected ChipSeq data from Shen et al. 2012 (17) for the architectural protein CTCF, promoter-related marks (RNA Polymerase II and H3K4me3) and enhancer-related histone modifications (H3K4me1 and H3K27ac).”
Statistical confidence estimation for Hi-C data reveals regulatory chromatin contacts (2014, methodology): “Both of the genes transcribed from these promoters ( Gucy1a3 , Gucy1b3 ), as well as a third gene that is 212 kb downstream from the Gucy1a3 promoter ( Map9 ), exhibit cortex-specific expression (Shen et al. 2012).”