Discovery and characterization of human exonic transcriptional regulatory elements.
We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs...
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2012
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oai:doaj.org-article:e7ddf6fd1694459392de2c899988137d2021-11-18T07:04:15ZDiscovery and characterization of human exonic transcriptional regulatory elements.1932-620310.1371/journal.pone.0046098https://doaj.org/article/e7ddf6fd1694459392de2c899988137d2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/23029400/?tool=EBIhttps://doaj.org/toc/1932-6203We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome.Arshad H KhanAndy LinDesmond J SmithPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 9, p e46098 (2012) |
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Medicine R Science Q Arshad H Khan Andy Lin Desmond J Smith Discovery and characterization of human exonic transcriptional regulatory elements. |
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We sought exonic transcriptional regulatory elements by shotgun cloning human cDNA fragments into luciferase reporter vectors and measuring the resulting expression levels in liver cells. We uncovered seven regulatory elements within coding regions and three within 3' untranslated regions (UTRs). Two of the putative regulatory elements were enhancers and eight were silencers. The regulatory elements were generally but not consistently evolutionarily conserved and also showed a trend toward decreased population diversity. Furthermore, the exonic regulatory elements were enriched in known transcription factor binding sites (TFBSs) and were associated with several histone modifications and transcriptionally relevant chromatin. Evidence was obtained for bidirectional cis-regulation of a coding region element within a tubulin gene, TUBA1B, by the transcription factors PPARA and RORA. We estimate that hundreds of exonic transcriptional regulatory elements exist, an unexpected finding that highlights a surprising multi-functionality of sequences in the human genome. |
format |
article |
author |
Arshad H Khan Andy Lin Desmond J Smith |
author_facet |
Arshad H Khan Andy Lin Desmond J Smith |
author_sort |
Arshad H Khan |
title |
Discovery and characterization of human exonic transcriptional regulatory elements. |
title_short |
Discovery and characterization of human exonic transcriptional regulatory elements. |
title_full |
Discovery and characterization of human exonic transcriptional regulatory elements. |
title_fullStr |
Discovery and characterization of human exonic transcriptional regulatory elements. |
title_full_unstemmed |
Discovery and characterization of human exonic transcriptional regulatory elements. |
title_sort |
discovery and characterization of human exonic transcriptional regulatory elements. |
publisher |
Public Library of Science (PLoS) |
publishDate |
2012 |
url |
https://doaj.org/article/e7ddf6fd1694459392de2c899988137d |
work_keys_str_mv |
AT arshadhkhan discoveryandcharacterizationofhumanexonictranscriptionalregulatoryelements AT andylin discoveryandcharacterizationofhumanexonictranscriptionalregulatoryelements AT desmondjsmith discoveryandcharacterizationofhumanexonictranscriptionalregulatoryelements |
_version_ |
1718424012476907520 |