Genomic identification of regulatory elements by evolutionary sequence comparison and functional analysis.
Despite remarkable recent advances in genomics that have enabled us to identify most of the genes in the human genome, comparable efforts to define transcriptional cis-regulatory elements that control gene expression are lagging behind. The difficulty of this task stems from two equally important problems: our knowledge of how regulatory elements are encoded in genomes remains elementary, and there is a vast genomic search space for regulatory elements, since most of mammalian genomes are noncoding. Comparative genomic approaches are having a remarkable impact on the study of transcriptional regulation in eukaryotes and currently represent the most efficient and reliable methods of predicting noncoding sequences likely to control the patterns of gene expression. By subjecting eukaryotic genomic sequences to computational comparisons and subsequent experimentation, we are inching our way toward a more comprehensive catalog of common regulatory motifs that lie behind fundamental biological processes. We are still far from comprehending how the transcriptional regulatory code is encrypted in the human genome and providing an initial global view of regulatory gene networks, but collectively, the continued development of comparative and experimental approaches will rapidly expand our knowledge of the transcriptional regulome.
Loots
Gabriela G
GG
Biosciences and Biotechnology Division, Chemistry, Materials and Life Sciences Directorate, Lawrence Livermore National Laboratory, Livermore, California 94550, USA.
D000818:Animals; D030801:Animals, Genetically Modified; D002874:Chromosome Mapping / Q000379:methods*; D019295:Computational Biology / Q000379:methods; D017124:Conserved Sequence / Q000502:physiology; D019143:Evolution, Molecular; D005786:Gene Expression Regulation; D030342:Genetic Diseases, Inborn / Q000235:genetics; D015894:Genome, Human / Q000502:physiology; D023281:Genomics / Q000379:methods; D006801:Humans; D051379:Mice; D008954:Models, Biological; D012045:Regulatory Sequences, Nucleic Acid / Q000235:genetics* / Q000502:physiology*; D054928:Validation Studies as Topic