Cell-specific exon methylation and CTCF binding in neurons regulate calcium ion channel splicing and function.

ABSTRACT: Cell-specific alternative splicing modulates myriad cell functions and is disrupted in disease. The mechanisms governing alternative splicing are known for relatively few genes and typically focus on RNA splicing factors. In sensory neurons, cell-specific alternative splicing of the presynaptic CaV channel Cacna1b gene modulates opioid sensitivity. How this splicing is regulated is unknown. We find that cell and exon-specific DNA hypomethylation permits CTCF binding, the master regulator of mammalian chromatin structure, which, in turn, controls splicing in a DRG-derived cell line. In vivo, hypomethylation of an alternative exon specifically in nociceptors, likely permits CTCF binding and expression of CaV2.2 channel isoforms with increased opioid sensitivity in mice. Following nerve injur

SUBMITTER: Lopez Soto EJ 

PROVIDER: S-EPMC7124252 | biostudies-literature | 2020 Mar

REPOSITORIES: biostudies-literature