RNA Polymerase II Elongation at the Crossroads of Transcription and Alternative Splicing

Figure 3

Chromatin couples elongation to alternative splicing. (a) Early evidence for a role of chromatin on splicing: replication affects alternative splicing. Loose nucleosome assembly (as in transiently transfected reporter minigenes) gives rise to low inclusion of the alternative exon (yellow) into the mature mRNA. After replication, nucleosome organization becomes more compact, promoting much higher inclusion of the alternative exon. (b) Depolarization of neuronal cells or treatment with TSA triggers intragenic histone acetylation and looser nucleosome compaction which in turn causes skipping of the alternative exon (yellow). (c) Model for TGS-AS. Transfection with siRNAs targeting the intron downstream from the alternative exon (yellow) promotes dimethylation and trimethylation of H3K9 and H3K27 (green and blue marks, resp.), triggered by siRNA’s guide strand entering a silencing complex containing AGO1. HP1α is recruited and the resulting condensed chromatin structure generates roadblocks to Pol II elongation, causing higher inclusion of the alternative exon according to the kinetic coupling model.