Mouse regulatory DNA landscapes reveal global principles of cis-regulatory evolution
By J. Vierstra, Eric Rynes, R. Sandstrom, Miaohua Zhang, T. Canfield, R. Hansen, Sandra Stehling-Sun, P. Sabo, Rachel Byron, R. Humbert and 27 more. 2014
264 citations recorded by the source corpus.
To study the evolutionary dynamics of regulatory DNA, we mapped >1.3 million deoxyribonuclease I–hypersensitive sites (DHSs) in 45 mouse cell and tissue types, and systematically compared these with human DHS maps from orthologous compartments. We found that the mouse and human genomes have undergone extensive cis-regulatory rewiring that combines branch-specific evolutionary innovation and loss with widespread repurposing of conserved DHSs to alternative cell fates, and that this process is mediated by turnover of transcription factor (TF) recognition elements. Despite pervasive evolutionary remodeling of the location and content of individual cis-regulatory regions, within orthologous mouse and human cell types the global fraction of regulatory DNA bases encoding recognition sites for each TF has been strictly conserved. Our findings provide new insights into the evolutionary forces shaping mammalian regulatory DNA landscapes. Mouse-to-human genomic comparisons illuminate conserved transcriptional programs despite regulatory rewiring. Rewiring the gene regulatory landscape DNAse I hypersensitive sites (DHSs) correlate with genomic locations that control where messenger RNA is to be produced. DHSs differ, depending on the cell type, developmental stage, and species. Viestra et al. compared mouse and human genome-wide DHS maps. Approximately one-third of the DHSs are conserved between the species, which separated approximately 550 million years ago. Most DHSs fell into tissue-specific cohorts; however, these were generally not conserved between the human and mouse. It seems that the majority of DHSs evolve because of changes in the sequence that gradually change how the region is regulated. Science, this issue p. 1007
Subfields: Molecular Biology
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Citations in the corpus
- Ever-changing landscapes: transcriptional enhancers in development and evolution (2016, background): “Recent genome-wide mapping of DNase hypersensitive sites (DHSs) (Vierstra et al., 2014) revealed that DHSs at orthologous loci between human andmouse were functionally active in distinct tissues, revealing frequent regulatory element repurposing across 90 million years of evolution.”
- A Single-Cell Atlas of In Vivo Mammalian Chromatin Accessibility. (2018, unknown): “Given the degree of conservation of chromatin accessibility between mice and humans (Vierstra et al., 2014), we wondered if we could use our data to better understand the cell-type-specific effects of genetic variation underlying complex human traits regardless of the differences between species.”