The functional modulation of epigenetic regulators by alternative splicing

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.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.Epigenetic regulation of gene expression constitutes a fundamental mechanism by which a series of chromatin modifications allow the normal functioning of the cell under different conditions [1-3]. 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 [4]. In agreement with this, an increasingly large amount of experimental data shows the relevance of chromatin modifications in development [5], disease [6], etc. For example, recent studies indicate that histone modifications are involved in paternal X chromosome inactivation [7,8]. Work from Roopra and colleagues [9] 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 [10].Chromatin modificatio