How are short exonic sequences recognized within the vast intronic oceans in 
which they reside? Despite decades of research, this remains one of the most 
fundamental, yet enigmatic, questions in the field of pre-mRNA splicing 
research. For many years, studies aiming to shed light on this process were 
focused at the RNA level, characterizing the manner by which splicing factors 
and auxiliary proteins interact with splicing signals, thereby enabling, 
facilitating and regulating splicing. However, we increasingly understand that 
splicing is not an isolated process; rather it occurs co-transcriptionally and 
is presumably also regulated by transcription-related processes. In fact, 
studies by our group and others over the past year suggest that DNA structure in 
terms of nucleosome positioning and specific histone modifications, which have a 
well established role in transcription, may also have a role in splicing. In 
this review we discuss evidence for the coupling between transcription and 
splicing, focusing on recent findings suggesting a link between chromatin 
structure and splicing, and highlighting challenges this emerging field is 
facing.