skip to main content
OSTI.GOV title logo U.S. Department of Energy
Office of Scientific and Technical Information

Title: In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences

Abstract

The identification of enhancers with predicted specificitiesin vertebrate genomes remains a significant challenge that is hampered bya lack of experimentally validated training sets. In this study, weleveraged extreme evolutionary sequence conservation as a filter toidentify putative gene regulatory elements and characterized the in vivoenhancer activity of human-fish conserved and ultraconserved1 noncodingelements on human chromosome 16 as well as such elements from elsewherein the genome. We initially tested 165 of these extremely conservedsequences in a transgenic mouse enhancer assay and observed that 48percent (79/165) functioned reproducibly as tissue-specific enhancers ofgene expression at embryonic day 11.5. While driving expression in abroad range of anatomical structures in the embryo, the majority of the79 enhancers drove expression in various regions of the developingnervous system. Studying a set of DNA elements that specifically droveforebrain expression, we identified DNA signatures specifically enrichedin these elements and used these parameters to rank all ~;3,400human-fugu conserved noncoding elements in the human genome. The testingof the top predictions in transgenic mice resulted in a three-foldenrichment for sequences with forebrain enhancer activity. These datadramatically expand the catalogue of in vivo-characterized human geneenhancers and illustrate the future utility of such training sets for avariety of iological applications including decoding the regulatoryvocabulary ofmore » the human genome.« less

Authors:
; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ; ;
Publication Date:
Research Org.:
Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
Sponsoring Org.:
USDOE Director, Office of Science; National Institutes ofHealth
OSTI Identifier:
919760
Report Number(s):
LBNL-59842
R&D Project: GHPG6B; BnR: 400412000; TRN: US200822%%524
DOE Contract Number:  
DE-AC02-05CH11231; NIHHL066681
Resource Type:
Journal Article
Resource Relation:
Journal Name: Nature; Journal Volume: 444; Journal Issue: 7118; Related Information: Journal Publication Date: 11/23/2006
Country of Publication:
United States
Language:
English
Subject:
60 APPLIED LIFE SCIENCES; CHROMOSOMES; DNA; GENES; HUMAN CHROMOSOME 16; IN VIVO; NERVOUS SYSTEM; TESTING; TRAINING; TRANSGENIC MICE; VERTEBRATES; In Vivo Enhancer Chromosome 16

Citation Formats

Pennacchio, Len A., Ahituv, Nadav, Moses, Alan M., Nobrega,Marcelo, Prabhakar, Shyam, Shoukry, Malak, Minovitsky, Simon, Visel,Axel, Dubchak, Inna, Holt, Amy, Lewis, Keith D., Plajzer-Frick, Ingrid, Akiyama, Jennifer, De Val, Sarah, Afzal, Veena, Black, Brian L., Couronne, Olivier, Eisen, Michael B., and Rubin, Edward M.. In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences. United States: N. p., 2006. Web. doi:10.1038/nature05295.
Pennacchio, Len A., Ahituv, Nadav, Moses, Alan M., Nobrega,Marcelo, Prabhakar, Shyam, Shoukry, Malak, Minovitsky, Simon, Visel,Axel, Dubchak, Inna, Holt, Amy, Lewis, Keith D., Plajzer-Frick, Ingrid, Akiyama, Jennifer, De Val, Sarah, Afzal, Veena, Black, Brian L., Couronne, Olivier, Eisen, Michael B., & Rubin, Edward M.. In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences. United States. doi:10.1038/nature05295.
Pennacchio, Len A., Ahituv, Nadav, Moses, Alan M., Nobrega,Marcelo, Prabhakar, Shyam, Shoukry, Malak, Minovitsky, Simon, Visel,Axel, Dubchak, Inna, Holt, Amy, Lewis, Keith D., Plajzer-Frick, Ingrid, Akiyama, Jennifer, De Val, Sarah, Afzal, Veena, Black, Brian L., Couronne, Olivier, Eisen, Michael B., and Rubin, Edward M.. Wed . "In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences". United States. doi:10.1038/nature05295. https://www.osti.gov/servlets/purl/919760.
@article{osti_919760,
title = {In Vivo Enhancer Analysis Chromosome 16 Conserved NoncodingSequences},
author = {Pennacchio, Len A. and Ahituv, Nadav and Moses, Alan M. and Nobrega,Marcelo and Prabhakar, Shyam and Shoukry, Malak and Minovitsky, Simon and Visel,Axel and Dubchak, Inna and Holt, Amy and Lewis, Keith D. and Plajzer-Frick, Ingrid and Akiyama, Jennifer and De Val, Sarah and Afzal, Veena and Black, Brian L. and Couronne, Olivier and Eisen, Michael B. and Rubin, Edward M.},
abstractNote = {The identification of enhancers with predicted specificitiesin vertebrate genomes remains a significant challenge that is hampered bya lack of experimentally validated training sets. In this study, weleveraged extreme evolutionary sequence conservation as a filter toidentify putative gene regulatory elements and characterized the in vivoenhancer activity of human-fish conserved and ultraconserved1 noncodingelements on human chromosome 16 as well as such elements from elsewherein the genome. We initially tested 165 of these extremely conservedsequences in a transgenic mouse enhancer assay and observed that 48percent (79/165) functioned reproducibly as tissue-specific enhancers ofgene expression at embryonic day 11.5. While driving expression in abroad range of anatomical structures in the embryo, the majority of the79 enhancers drove expression in various regions of the developingnervous system. Studying a set of DNA elements that specifically droveforebrain expression, we identified DNA signatures specifically enrichedin these elements and used these parameters to rank all ~;3,400human-fugu conserved noncoding elements in the human genome. The testingof the top predictions in transgenic mice resulted in a three-foldenrichment for sequences with forebrain enhancer activity. These datadramatically expand the catalogue of in vivo-characterized human geneenhancers and illustrate the future utility of such training sets for avariety of iological applications including decoding the regulatoryvocabulary of the human genome.},
doi = {10.1038/nature05295},
journal = {Nature},
number = 7118,
volume = 444,
place = {United States},
year = {Wed Feb 01 00:00:00 EST 2006},
month = {Wed Feb 01 00:00:00 EST 2006}
}