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Nat Rev Genet. 2012 Jun 18;13(7):469-83. doi: 10.1038/nrg3242.

Genomic approaches towards finding cis-regulatory modules in animals.

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Department of Biochemistry and Molecular Biology, Center for Comparative Genomics and Bioinformatics, 304 Wartik Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.


Differential gene expression is the fundamental mechanism underlying animal development and cell differentiation. However, it is a challenge to identify comprehensively and accurately the DNA sequences that are required to regulate gene expression: namely, cis-regulatory modules (CRMs). Three major features, either singly or in combination, are used to predict CRMs: clusters of transcription factor binding site motifs, non-coding DNA that is under evolutionary constraint and biochemical marks associated with CRMs, such as histone modifications and protein occupancy. The validation rates for predictions indicate that identifying diagnostic biochemical marks is the most reliable method, and understanding is enhanced by the analysis of motifs and conservation patterns within those predicted CRMs.

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