Human-specific gain of function in a developmental enhancer. Export

@article{citeulike:3196493, abstract = {Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain.}, author = {Prabhakar, Shyam and Visel, Axel and Akiyama, Jennifer A. and Shoukry, Malak and Lewis, Keith D. and Holt, Amy and Plajzer-Frick, Ingrid and Morrison, Harris and Fitzpatrick, David R. and Afzal, Veena and Pennacchio, Len A. and Rubin, Edward M. and Noonan, James P.}, citeulike-article-id = {3196493}, citeulike-linkout-0 = {http://dx.doi.org/10.1126/science.1159974}, citeulike-linkout-1 = {http://www.sciencemag.org/cgi/content/abstract/321/5894/1346}, citeulike-linkout-2 = {http://view.ncbi.nlm.nih.gov/pubmed/18772437}, citeulike-linkout-3 = {http://www.hubmed.org/display.cgi?uids=18772437}, day = {5}, doi = {10.1126/science.1159974}, issn = {1095-9203}, journal = {Science (New York, N.Y.)}, keywords = {cns-differences, cns-similarity, mutations, notconserved}, month = {September}, number = {5894}, pages = {1346--1350}, posted-at = {2008-09-05 10:48:07}, priority = {2}, title = {Human-specific gain of function in a developmental enhancer.}, url = {http://dx.doi.org/10.1126/science.1159974}, volume = {321}, year = {2008} }

TY - JOUR ID - citeulike:3196493 L3 - citeulike-article-id:3196493 N2 - Changes in gene regulation are thought to have contributed to the evolution of human development. However, in vivo evidence for uniquely human developmental regulatory function has remained elusive. In transgenic mice, a conserved noncoding sequence (HACNS1) that evolved extremely rapidly in humans acted as an enhancer of gene expression that has gained a strong limb expression domain relative to the orthologous elements from chimpanzee and rhesus macaque. This gain of function was consistent across two developmental stages in the mouse and included the presumptive anterior wrist and proximal thumb. In vivo analyses with synthetic enhancers, in which human-specific substitutions were introduced into the chimpanzee enhancer sequence or reverted in the human enhancer to the ancestral state, indicated that 13 substitutions clustered in an 81-base pair module otherwise highly constrained among terrestrial vertebrates were sufficient to confer the human-specific limb expression domain. IS - 5894 JF - Science (New York, N.Y.) SN - 1095-9203 EP - 1350 TI - Human-specific gain of function in a developmental enhancer. VL - 321 SP - 1346 KW - cns-differences KW - cns-similarity KW - mutations KW - notconserved AU - Prabhakar, Shyam AU - Visel, Axel AU - Akiyama, Jennifer AU - Shoukry, Malak AU - Lewis, Keith AU - Holt, Amy AU - Plajzer-Frick, Ingrid AU - Morrison, Harris AU - Fitzpatrick, David AU - Afzal, Veena AU - Pennacchio, Len AU - Rubin, Edward AU - Noonan, James PY - 2008/09/05/ UR - http://dx.doi.org/10.1126/science.1159974 ER -