A WWW supplement to:

Computation-based discovery of related transcriptional regulatory modules and motifs using an experimentally validated combinatorial model

 

Marc S. Halfon*1, Yonatan Grad*2, George M. Church2 and Alan M. Michelson1, 3

 

1Howard Hughes Medical Institute and Department of Medicine, Brigham and Women’s Hospital, Boston, MA 02115

 

2Department of Genetics, Harvard Medical School, and

Lipper Center for Computational Genetics, Boston, MA 02115

 

*These authors contributed equally to this work



 

Abstract

Gene expression is regulated by transcription factors that interact with cis-regulatory elements. Predicting these elements from sequence data has proven difficult. We describe here a successful computational search for elements that direct expression in a particular temporal-spatial pattern in the Drosophila embryo, based on a single well characterized enhancer model. The fly genome was searched to identify sequence elements containing the same combination of transcription factors as those found in the model. Experimental evaluation of the search results demonstrates that our method can correctly predict regulatory elements and highlights the importance of functional testing as a means of identifying false-positive results. We also show that the search results enable the identification of additional relevant sequence motifs whose functions can be empirically validated. This approach, combined with gene expression and phylogenetic sequence data, allows for genome-wide identification of related regulatory elements, an important step toward understanding the genetic regulatory networks involved in development.

Web Table 1

Web Table 2

Web Figure 1

Web Figure 2

AlignACE, ScanACE, and other ACE package programs are available here.

The program used to perform the combinatorial search is available for download here. 

For questions about the cooccur_scan.pl program or the computational methods, please contact Yonatan Grad.


Contacts


Correspondence regarding this paper may be addressed to Alan Michelson at:
phone: (617) 732-7411

fax: (617) 738-5575

e-mail: michelson@rascal.med.harvard.edu

 

Or e-mail:

 

Marc Halfon

Yonatan Grad

George Church