e in public databases. We found that 49 % 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 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 DM-1 control the transcriptional state of large sets of genes, we propose that epigenetic regulation of gene expression is itself strongly regulated by alternative splicing. Background Epigenetic regulation of gene expression constitutes a fundamental mechanism by which a series of chromatin modifications allow the normal PubMed ID:http://www.ncbi.nlm.nih.gov/pubmed/19796427 functioning of the cell under different conditions. In particular, these modifications control the repressive effect of chromatin, which limits the access of regulatory proteins to DNA, thus posing serious restraints to biological processes like replication, transcription, etc. In agreement with this, an increasingly large amount of experimental data shows the relevance of chromatin modifications in development, disease, etc. For example, recent studies indicate that Page 1 of 14 BMC Genomics 2007, 8:252 http://www.biomedcentral.com/1471-2164/8/252 histone modifications are involved in paternal X chromosome inactivation. Work from Roopra and colleagues shows that histone methylation regulates the tissue-dependent silencing of neuronal genes. Also, expression of Hox transcription factors is directly related to the presence of histone marks. Chromatin modifications are produced by a series of chromatin-modifying enzymes that act on chromatin by either introducing histone modifications or by inducing ATP-dependent nucleosome remodelling. Histone modifications usually take place at histone tails and can introduce a wide variety of covalent marks including acetylation, methylation, phosphorylation, etc. These marks provide a simple way to access nucleosomal DNA and normally have different functional consequences. A synthetic view of the biological role of histone modifications is provided by the histone code hypothesis. According to this hypothesis, the regulatory state of a gene is a function of these modifications and their combinations. Apart from histone-modifying enzymes, enzymes that utilise ATP to modify the nucleosomal structure, altering histone-DNA interactions, also give access to nucleosomal DNA. Interestingly, both mechanisms are coordinated and cooperate to finally give access to nucleosomal DNA. For example, it has been recently shown that the SWI/SNF complex is retained to the chromatin only if SAGA or NuA4 
acetylate it. As with transcription factors, the functional activity of chromatin-modifying enzymes must be regulated in order to produce gene expression patterns that are coherent with high-level biological processes, like development or tissue differentiation. However, little is yet known about how this regulation occurs, due to the recent discovery of these enzymes. Among the possible regulation levels, like transcription, translation or mRNA splicing, in this work we have focused on the study of the latter. We have chosen alternative splicing for four different reasons. First, because recent data strongly suggest that alternative splicing can introduce functionall