Phylogenetic footprinting: an evolutionary tool for the identification of cis-regulatory elements

Hozana A. Castillo, Carla V. C. Grade, Susanne Dietrich, Frank Schubert, Monica S. Salerno, Jose Xavier-Neto, Lucia E. Alvares

Research output: Chapter in Book/Report/Conference proceedingChapter (peer-reviewed)


Phylogenetic footprinting is an evolutionary tool used for the identification of functional elements in selected genomes. This method relies on the search for similarities among ancestrally related sequences and has been widely used to identify cis-regulatory elements in non-coding genomic regions. Conserved
non-coding elements (CNEs) have been shown to be crucial for controlling gene transcription in vertebrate genomes. Here we present practical guidelines for discovering new cis-regulatory elements using phylogenetic footprinting and discuss pros and cons of different approaches for the functional characterization of
these elements. In addition, we present two case studies to provide practical examples of how this powerful technique is used. The first case study illustrates the in silico identification of the Myostatin gene promoter conserved in vertebrates and its biological validation. The second case study describes the search
for cis-regulatory elements of the Raldh2 gene and demonstrates the conserved biological function of an intronic CNE responsible for modulating the gene activity in the embryonic dorsal spinal cord in vertebrates. The comparison of these two case studies highlights the similarities and differences regarding bioinformatic
strategies and validation methods for the identification and functional characterization of promoters and distal cis-regulatory elements (enhancers/silencers).
Original languageEnglish
Title of host publicationThe analysis of regulatory DNA
Subtitle of host publicationcurrent developments, knowledge and applications uncovering gene regulation
EditorsKenneth W. Berendzen, Joachim Kilian, Dierk Wanke
PublisherBentham Science
ISBN (Electronic)9781608054923
ISBN (Print)9781608057115
Publication statusPublished - 2013


  • Phylogenetic footprinting
  • Conserved non-coding elements
  • Enhancer
  • Myostatin
  • Retinaldehyde Dehydrogenase 2


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