CTCF-promoted RNA polymerase II pausing links DNA methylation to splicing

There are emerging links between gene transcription and alternative pre-mRNA splicing. For example, spliceosome assembly is thought to occur on the nascent RNA as it is being transcribed, and the rate of transcription elongation has been linked to splicing. Shukla et al. show that the DNA-binding protein CTCF can promote inclusion of exons with weak splice sites, through a mechanism that involves pausing of RNA polymerase II. Because CTCF binding to DNA is influenced by DNA methylation, this raises the possibility that DNA methylation patterns during development could contribute to alternative splicing outcomes.