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Briefings in Functional Genomics and Proteomics Advance Access published online on June 4, 2009
Briefings in Functional Genomics and Proteomics, doi:10.1093/bfgp/elp014
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Published by Oxford University Press 2009. For permissions, please email: journals.permissions@oxfordjournals.org

Technique Review

Identifying regulatory elements in eukaryotic genomes

Leelavati Narlikar and Ivan Ovcharenko

Corresponding author. Ivan Ovcharenko, Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health (NIH), Bethesda, MD, USA. Tel: (301) 435-8944; Fax: (301) 480-2290; Zip Code: 20894; E-mail: ovcharei{at}ncbi.nlm.nih.gov


Leelavati Narlikar is a postdoctoral fellow at the Computational Biology Branch of the National Center for Biotechnology Information (NCBI), National Library of Medicine (NLM), National Institutes of Health (NIH). Her research interests include modeling the architecture of tissue-specific enhancers and developing computational techniques to identify novel regulatory elements.


Ivan Ovcharenko is a Principal Investigator at the Computational Biology Branch of the National Center for Biotechnology Information (NCBI), National Library of Medicine (NLM), National Institutes of Health (NIH). His research is focused on the computational analysis of gene regulation in the human and other vertebrate genomes. Ovcharenko laboratory is particularly interested in determining the genomic code of tissue-specific regulatory elements, evolutionary divergence of enhancers and silencers, population variation in non-coding DNA and non-coding polymorphisms associated with genetic disorders.

Proper development and functioning of an organism depends on precise spatial and temporal expression of all its genes. These coordinated expression-patterns are maintained primarily through the process of transcriptional regulation. Transcriptional regulation is mediated by proteins binding to regulatory elements on the DNA in a combinatorial manner, where particular combinations of transcription factor binding sites establish specific regulatory codes. In this review, we survey experimental and computational approaches geared towards the identification of proximal and distal gene regulatory elements in the genomes of complex eukaryotes. Available approaches that decipher the genetic structure and function of regulatory elements by exploiting various sources of information like gene expression data, chromatin structure, DNA-binding specificities of transcription factors, cooperativity of transcription factors, etc. are highlighted. We also discuss the relevance of regulatory elements in the context of human health through examples of mutations in some of these regions having serious implications in misregulation of genes and being strongly associated with human disorders.

Keywords: transcriptional regulation, enhancers, silencers, tissue-specific regulatory elements, population variation, non-coding diseases, computational analysis of regulatory element sequence composition


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