title: The evolution of lineage-specific regulatory activities in the human embryonic limb.
abstract: 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.
authors.affiliation: Department of Genetics, Yale University School of Medicine, New Haven, CT 06520, USA.
authors.forename: Justin
authors.initials: J
authors.lastname: Cotney
authors.forename: Jing
authors.initials: J
authors.lastname: Leng
authors.forename: Jun
authors.initials: J
authors.lastname: Yin
authors.forename: Steven K
authors.initials: SK
authors.lastname: Reilly
authors.forename: Laura E
authors.initials: LE
authors.lastname: DeMare
authors.forename: Deena
authors.initials: D
authors.lastname: Emera
authors.forename: Albert E
authors.initials: AE
authors.lastname: Ayoub
authors.forename: Pasko
authors.initials: P
authors.lastname: Rakic
authors.forename: James P
authors.initials: JP
authors.lastname: Noonan
mesh_terms: D000107:Acetylation; D000818:Animals; D005075:Biological Evolution; D004742:Enhancer Elements, Genetic; D005121:Extremities / Q000196:embryology*; D018507:Gene Expression Regulation, Developmental; D005826:Genetics, Medical; D055106:Genome-Wide Association Study; D006657:Histones / Q000378:metabolism; D006801:Humans; D008253:Macaca mulatta / Q000196:embryology; D051379:Mice / Q000196:embryology; D038081:Organogenesis; D011401:Promoter Regions, Genetic; D059467:Transcriptome
chemical_list: D006657:Histones