Predicting Tissue-Specific Enhancers in the Human Genome

Journal Article · Sat Jul 01 04:00:00 EDT 2006 · Nature Biotechnology

OSTI ID:919377

Pennacchio, Len A; Loots, Gabriela G; Nobrega, Marcelo A; Ovcharenko, Ivan

Determining how transcriptional regulatory signals areencoded in vertebrate genomes is essential for understanding the originsof multi-cellular complexity; yet the genetic code of vertebrate generegulation remains poorly understood. In an attempt to elucidate thiscode, we synergistically combined genome-wide gene expression profiling,vertebrate genome comparisons, and transcription factor binding siteanalysis to define sequence signatures characteristic of candidatetissue-specific enhancers in the human genome. We applied this strategyto microarray-based gene expression profiles from 79 human tissues andidentified 7,187 candidate enhancers that defined their flanking geneexpression, the majority of which were located outside of knownpromoters. We cross-validated this method for its ability to de novopredict tissue-specific gene expression and confirmed its reliability in57 of the 79 available human tissues, with an average precision inenhancer recognition ranging from 32 percent to 63 percent, and asensitivity of 47 percent. We used the sequence signatures identified bythis approach to assign tissue-specific predictions to ~;328,000human-mouse conserved noncoding elements in the human genome. Byoverlapping these genome-wide predictions with a large in vivo dataset ofenhancers validated in transgenic mice, we confirmed our results with a28 percent sensitivity and 50 percent precision. These results indicatethe power of combining complementary genomic datasets as an initialcomputational foray into the global view of tissue-specific generegulation in vertebrates.

• Research Organization: Ernest Orlando Lawrence Berkeley NationalLaboratory, Berkeley, CA (US)
• Sponsoring Organization: USDOE Director, Office of Science; National Institutes ofHealth
• DOE Contract Number: AC02-05CH11231
• OSTI ID: 919377
• Report Number(s): LBNL--61287
• Journal Information: Nature Biotechnology, Journal Name: Nature Biotechnology Journal Issue: 2 Vol. 17; ISSN NABIF9; ISSN 1087-0156
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ANIMAL TISSUES
GENE REGULATION
GENES
GENETICS
IN VIVO
PROMOTERS
RELIABILITY
SENSITIVITY
TRANSCRIPTION FACTORS
TRANSGENIC MICE
VERTEBRATES