The Worlds of Splicing and Chromatin Collide

Both transcription and splicing take place in a nuclear environment which, at face value, may seem refractory to the efficiency afforded by the coupling of both processes. This environment, chromatin, was once viewed as only a passive packaging system for genetic material, with very little contribution to the variety of nuclear activities occurring within and around it. However, overwhelming evidence now points to the chromatin environment as being highly dynamic, and an active player in nuclear activities. Residues on all four histone N-termini (also known as tails) have been shown to be post-translationally modified in a variety of ways. Many of these modifications have been found to be recognized by factors involved in the regulation of gene expression and are associated with particular activating or repressive states, leading to the proposal of a “histone code” that directs (contributes to) the activity of gene regulatory factors ([1]). In addition to compositional changes, chromatin structure has also been proven to be dynamic. Specific enzymes have been characterized to utilize the energy from ATP hydrolysis to physically disrupt histoneDNA contacts, “remodeling” chromatin and altering the accessibility of DNA ([2]). These chromatin remodelers can slide nucleosomes along the DNA template, and even remove individual or subset of histones or entire nucleosomes at a particular genetic locus. In addition to changes in nucleosome (histone octamer plus 146 base-pairs of DNA) density at the primary level, chromatin structure can also be altered at a secondary level, exhibiting the ability to form compacted (and de-compacted) structures. Overall, the role of chromatin and factors acting upon it in the regulation of transcription (generally referred to as epigenetics) has become a well-studied topic, and a much better understanding of gene regulation has lead to many important breakthroughs in the fields of cellular differentiation, development, and disease. Because of the popularity of epigenetics and the knowledge that transcription and splicing are not mutually-exclusive, the role of chromatin in splicing is becoming an important area of research foci as well.