Functional autonomy of distant-acting human enhancers

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Many human genes are associated with dispersed arrays of transcriptional enhancers that regulate their expression in time and space. Studies in invertebrate model systems have suggested that these elements function as discrete and independent regulatory units, but the in vivo combinatorial properties of vertebrate enhancers remain poorly understood. To explore the modularity and regulatory autonomy of human developmental enhancers, we experimentally concatenated up to four enhancers from different genes and used a transgenic mouse assay to compare the in vivo activity of these compound elements with that of the single modules. In all of the six different combinations of elements ... continued below

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Visel, Axel; Akiyama, Jennifer A.; Shoukry, Malak; Afzal, Veena; Rubin, Edward M. & Pennacchio, Len A. February 19, 2009.

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Many human genes are associated with dispersed arrays of transcriptional enhancers that regulate their expression in time and space. Studies in invertebrate model systems have suggested that these elements function as discrete and independent regulatory units, but the in vivo combinatorial properties of vertebrate enhancers remain poorly understood. To explore the modularity and regulatory autonomy of human developmental enhancers, we experimentally concatenated up to four enhancers from different genes and used a transgenic mouse assay to compare the in vivo activity of these compound elements with that of the single modules. In all of the six different combinations of elements tested, the reporter gene activity patterns were additive without signs of interference between the individual modules, indicating that regulatory specificity was maintained despite the presence of closely-positioned heterologous enhancers. Even in cases where two elements drove expression in close anatomical proximity, such as within neighboring subregions of the developing limb bud, the compound patterns did not show signs of cross-inhibition between individual elements or novel expression sites. These data indicate that human developmental enhancers are highly modular and functionally autonomous and suggest that genomic enhancer shuffling may have contributed to the evolution of complex gene expression patterns in vertebrates

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  • Journal Name: Genomics; Journal Volume: 93; Journal Issue: 6; Related Information: Journal Publication Date: 2009

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  • Report No.: LBNL-2256E
  • Grant Number: DE-AC02-05CH11231
  • Grant Number: LB07002033
  • Office of Scientific & Technical Information Report Number: 970570
  • Archival Resource Key: ark:/67531/metadc927427

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  • February 19, 2009

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  • Nov. 13, 2016, 7:26 p.m.

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  • Nov. 18, 2016, 2:44 p.m.

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Visel, Axel; Akiyama, Jennifer A.; Shoukry, Malak; Afzal, Veena; Rubin, Edward M. & Pennacchio, Len A. Functional autonomy of distant-acting human enhancers, article, February 19, 2009; Berkeley, California. (digital.library.unt.edu/ark:/67531/metadc927427/: accessed December 10, 2018), University of North Texas Libraries, Digital Library, digital.library.unt.edu; crediting UNT Libraries Government Documents Department.