Slight variations in the SC35 ESE sequence motif among human chromosomes: a computational approach

Gene expression is initiated by the binding of transcription factors to cis-regulatory modules such as enhancer elements binding to the Serine/Arginine proteins. Recently, we noticed an increased ability to identify the location as well as the motifs of enhancers using genome-wide information on spliceosomal factor occupancy, cofactor recruitment and chromatin modifications. In this study, we have undertaken a large-scale genomic analysis in an attempt to uncover if the exonic splicing enhancer motif binding to the SC35 and the SRp40 SR proteins is conserved among several groups of human genes. For the SRp40, the results showed that the ESE consensus is conserved among human genes. Concerning the SC35 SR protein, results showed an ESE motif conserved among human tissues and between different levels of muscular cell differentiation and within the same chromosome. However, this motif displays subtle discrepancies between genes localized in different chromosomes. These results emphasize the presence of different translational isoforms of the SFRS2 gene encoding for the SC35, or different post-translational protein maturations in different chromosomes, confirming that chromatin structure is another layer of gene regulation. These links between chromatin pattern and splicing give further mechanistic support to functional interconnections between splicing, transcription and chromatin structure, and raise the intriguing possibility of the existence of a memory for splicing patterns to be inherited through epigenetic modifications.