Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer.

@article{portnoy05, abstract = {The identification of noncoding functional elements within vertebrate genomes, such as those that regulate gene expression, is a major challenge. Comparisons of orthologous sequences from multiple species are effective at detecting highly conserved regions and can reveal potential regulatory sequences. The GDF6 gene controls developmental patterning of skeletal joints and is associated with numerous, distant cis-acting regulatory elements. Using sequence data from 14 vertebrate species, we performed novel multispecies comparative analyses to detect highly conserved sequences flanking GDF6. The complementary tools WebMCS and ExactPlus identified a series of multispecies conserved sequences (MCSs). Of particular interest are MCSs within noncoding regions previously shown to contain GDF6 regulatory elements. A previously reported conserved sequence at -64 kb was also detected by both WebMCS and ExactPlus. Analysis of LacZ-reporter transgenic mice revealed that a 440-bp segment from this region contains an enhancer for Gdf6 expression in developing proximal limb joints. Several other MCSs represent candidate GDF6 regulatory elements; many of these are not conserved in fish or frog, but are strongly conserved in mammals.}, address = {Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA.}, author = {Portnoy, Matthew E. E. and Mcdermott, Kelly J. J. and Antonellis, Anthony and Margulies, Elliott H. H. and Prasad, Arjun B. B. and Kingsley, David M. M. and Green, Eric D. D. and Mortlock, Douglas P. P. }, citeulike-article-id = {276973}, doi = {http://dx.doi.org/10.1016/j.ygeno.2005.05.003}, issn = {0888-7543}, journal = {Genomics}, keywords = {comparative\_genomics, element, enhancer, exactplus, gdf6, joint, mcs, regulatory}, month = {June}, posted-at = {2005-08-08 22:06:43}, priority = {0}, title = {Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer.}, url = {http://dx.doi.org/10.1016/j.ygeno.2005.05.003}, year = {2005} }

TY - JOUR ID - portnoy05 L3 - citeulike-article-id:276973 N2 - The identification of noncoding functional elements within vertebrate genomes, such as those that regulate gene expression, is a major challenge. Comparisons of orthologous sequences from multiple species are effective at detecting highly conserved regions and can reveal potential regulatory sequences. The GDF6 gene controls developmental patterning of skeletal joints and is associated with numerous, distant cis-acting regulatory elements. Using sequence data from 14 vertebrate species, we performed novel multispecies comparative analyses to detect highly conserved sequences flanking GDF6. The complementary tools WebMCS and ExactPlus identified a series of multispecies conserved sequences (MCSs). Of particular interest are MCSs within noncoding regions previously shown to contain GDF6 regulatory elements. A previously reported conserved sequence at -64 kb was also detected by both WebMCS and ExactPlus. Analysis of LacZ-reporter transgenic mice revealed that a 440-bp segment from this region contains an enhancer for Gdf6 expression in developing proximal limb joints. Several other MCSs represent candidate GDF6 regulatory elements; many of these are not conserved in fish or frog, but are strongly conserved in mammals. JF - Genomics SN - 0888-7543 AD - Genome Technology Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892, USA. TI - Detection of potential GDF6 regulatory elements by multispecies sequence comparisons and identification of a skeletal joint enhancer. KW - comparative_genomics KW - element KW - enhancer KW - exactplus KW - gdf6 KW - joint KW - mcs KW - regulatory AU - Portnoy, Matthew AU - Mcdermott, Kelly AU - Antonellis, Anthony AU - Margulies, Elliott AU - Prasad, Arjun AU - Kingsley, David AU - Green, Eric AU - Mortlock, Douglas PY - 2005/June/23/ UR - http://dx.doi.org/10.1016/j.ygeno.2005.05.003 ER -