Identifying regulatory elements in eukaryotic genomes.
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.
Narlikar
Leelavati
L
Computational Biology Branch, National Center for Biotechnology Information, National Library of Medicine, National Institutes of Health, Bethesda, MD 20894, USA.
Ovcharenko
Ivan
I
D000818:Animals; D019295:Computational Biology; D005057:Eukaryotic Cells / Q000378:metabolism*; D005786:Gene Expression Regulation; D016678:Genome / Q000235:genetics*; D006262:Health; D006801:Humans; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics*