Comparative Analysis Identifies Exonic Splicing Regulatory Sequences-The Complex Definition of Enhancers and Silencers

Amir Goren, Oren Ram, Maayan Amit, Hadas Keren, Galit Lev-Maor, Ida Vig, Tal Pupko, Gil Ast*

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

254 Scopus citations


Exonic splicing regulatory sequences (ESRs) are cis-acting factor binding sites that regulate constitutive and alternative splicing. A computational method based on the conservation level of wobble positions and the overabundance of sequence motifs between 46,103 human and mouse orthologous exons was developed, identifying 285 putative ESRs. Alternatively spliced exons that are either short in length or contain weak splice sites show the highest conservation level of those ESRs, especially toward the edges of exons. ESRs that are abundant in those subgroups show a different distribution between constitutively and alternatively spliced exons. Representatives of these ESRs and two SR protein binding sites were shown, experimentally, to display variable regulatory effects on alternative splicing, depending on their relative locations in the exon. This finding signifies the delicate positional effect of ESRs on alternative splicing regulation.

Original languageAmerican English
Pages (from-to)769-781
Number of pages13
JournalMolecular Cell
Issue number6
StatePublished - 23 Jun 2006
Externally publishedYes

Bibliographical note

Funding Information:
This effort was supported by the University of Kentucky, Lexington, Kentucky, through internal funding. The authors wish to thank the 3M Industrial Products Division, St. Paul, Minnesota, for their donation of FC-72. The authors also acknowledge the efforts of Donald Brigner whose patience and diligence allowed much of the data to be obtained.


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