Journal
CELL
Volume 154, Issue 1, Pages 185-196Publisher
CELL PRESS
DOI: 10.1016/j.cell.2013.05.056
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Funding
- National Institutes of Health [GM094780, DA023999, NS014841]
- Edward J. Mallinckrodt Jr. Foundation
- Rudolph Andersen Fellowship
- Howard Hughes Medical Research Scholars Fellowship
- NSF Graduate Research Fellowship
- Medical Research Council [G0700089, MC_PC_15004] Funding Source: researchfish
- MRC [G0700089, MC_PC_15004] Funding Source: UKRI
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The evolution of human anatomical features likely involved changes in gene regulation during development. However, the nature and extent of human-specific developmental regulatory functions remain unknown. We obtained a genome-wide view of cis-regulatory evolution in human embryonic tissues by comparing the histone modification H3K27ac, which provides a quantitative readout of promoter and enhancer activity, during human, rhesus, and mouse limb development. Based on increased H3K27ac, we find that 13% of promoters and 11% of enhancers have gained activity on the human lineage since the human-rhesus divergence. These gains largely arose by modification of ancestral regulatory activities in the limb or potential co-option from other tissues and are likely to have heterogeneous genetic causes. Most enhancers that exhibit gain of activity in humans originated in mammals. Gains at promoters and enhancers in the human limb are associated with increased gene expression, suggesting they include molecular drivers of human morphological evolution.
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