Alternative splicing affects more than 90% of human genes. Coupling between 
transcription and splicing has become crucial in the complex network underlying 
alternative splicing regulation. Because chromatin is the real template for 
nuclear transcription, changes in its structure, but also in the "reading" and 
"writing" of the histone code, could modulate splicing choices. Here, we discuss 
the evidence supporting these ideas, from the first proposal of chromatin 
affecting alternative splicing, performed 20 years ago, to the latest findings 
including genome-wide evidence that nucleosomes are preferentially positioned in 
exons. We focus on two recent reports from our laboratories that add new 
evidence to this field. The first report shows that a physiological stimulus 
such as neuron depolarization promotes intragenic histone acetylation (H3K9ac) 
and chromatin relaxation, causing the skipping of exon 18 of the neural cell 
adhesion molecule gene. In the second report, we show how specific histone 
modifications can be created at targeted gene regions as a way to affect 
alternative splicing: Using small interfering RNAs (siRNAs), we increased the 
levels of H3K9me2 and H3K27me3 in the proximity of alternative exon 33 of the 
human fibronectin gene, favoring its inclusion into mature messenger RNA (mRNA) 
through a mechanism that recalls RNA-mediated transcriptional gene silencing.