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Open Access Highly Accessed Research article

The functional modulation of epigenetic regulators by alternative splicing

Sergio Lois12, Noemí Blanco12, Marian Martínez-Balbás12* and Xavier de la Cruz23*

Author Affiliations

1 Instituto de Biología Molecular de Barcelona. CID. Consejo Superior de Investigaciones Científicas (CSIC); 08028 Barcelona, Spain

2 Institut de Recerca Biomèdica-PCB; 08028 Barcelona, Spain

3 Institució Catalana de Recerca i Estudis Avançats (ICREA); Barcelona, Spain

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BMC Genomics 2007, 8:252  doi:10.1186/1471-2164-8-252

Published: 25 July 2007

Abstract

Background

Epigenetic regulators (histone acetyltransferases, methyltransferases, chromatin-remodelling enzymes, etc) play a fundamental role in the control of gene expression by modifying the local state of chromatin. However, due to their recent discovery, little is yet known about their own regulation. This paper addresses this point, focusing on alternative splicing regulation, a mechanism already known to play an important role in other protein families, e.g. transcription factors, membrane receptors, etc.

Results

To this end, we compiled the data available on the presence/absence of alternative splicing for a set of 160 different epigenetic regulators, taking advantage of the relatively large amount of unexplored data on alternative splicing available in public databases. We found that 49 % (70 % in human) of these genes express more than one transcript. We then studied their alternative splicing patterns, focusing on those changes affecting the enzyme's domain composition. In general, we found that these sequence changes correspond to different mechanisms, either repressing the enzyme's function (e.g. by creating dominant-negative inhibitors of the functional isoform) or creating isoforms with new functions.

Conclusion

We conclude that alternative splicing of epigenetic regulators can be an important tool for the function modulation of these enzymes. Considering that the latter control the transcriptional state of large sets of genes, we propose that epigenetic regulation of gene expression is itself strongly regulated by alternative splicing.