Chromatin and Alternative Splicing

MARIANO ALLÓ*1, IGNACIO E. SCHOR*1, MANUEL J. MUÑOZ*1, MANUEL DE LA MATA#1, ENERITZ AGIRRE2, JUAN VALCÁRCEL3, EDUARDO EYRAS2 AND ALBERTO R. KORNBLIHTT

Cold Spring Harbor Laboratory, NY, EEUU

Simposio; Nuclear Organization & Function, 75th Cold Spring Harbor Symposium; 2010

Alternative splicing (AS) affects more than 70% of human genes.  Coupling between transcription and splicing has become a crucial step in the complex network of alternative splicing regulation. Plenty of examples have shown that the former could affect the latter and vice versa. As chromatin is the real template where transcription occurs, changes in its structure but also in its “read” and “writing” code could modify qualitatively and quantitatively splicing choices. Here we discuss the evidence supporting these ideas, from the first proof of chromatin structure affecting AS proposed 20 years ago to the newest findings.  We focus on two recent reports from our lab adding new evidence to this field. In the first one, we show that a physiological stimulus such as neuron depolarization could cause an intragenic augment of histone acetylation (H3K9ac) and chromatin relaxation causing the skipping of exon 18 of Neural Cell Adhesion Molecule gene. In the second one, we reveal the first evidence showing that we could write “the histone code” and affect AS. Using small interference RNAs we increased the levels of H3K9me2 and H3K27me3 in proximity to alternative exon EDI of human fibronectin gene favoring its recognition.