Nature Reviews Genetics 13, 469-483 (July 2012) | doi:10.1038/nrg3242

Article series: Regulatory elements

Genomic approaches towards finding cis-regulatory modules in animals

Ross C. Hardison1 & James Taylor2  About the authors


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.

Author affiliations

  1. Department of Biochemistry and Molecular Biology, Center for Comparative Genomics and Bioinformatics, 304 Wartik Laboratory, The Pennsylvania State University, University Park, Pennsylvania 16802, USA.
  2. Departments of Biology and Mathematics and Computer Science, Emory University, O. Wayne Rollins Research Center, 1510 Clifton Road NE, Atlanta, Georgia 30322, USA.

Correspondence to: Ross C. Hardison1 Email:

Correspondence to: James Taylor2 Email:

Published online 18 June 2012