Role of Rnf40-dependent histone monoubiquitination in peripheral nervous system myelination [ChIP-Seq]

To address the role of monoubiquitination of histone H2B at lysine 120 (H2Bub1), we inactivated the responsible E3 ligase by deleting Rnf40 in developing Schwann cells. Rnf40 becomes important for proper Schwann cell development shortly before and during differentiation. Its absence in Schwann cells leads to a peripheral neuropathy. ChIP-Seq studies with H2Bub1-specific antibodies were performed on sciatic nerves from control mice and mice with a Schwann cell-specific deletion of Rnf40 to detect alterations in genomic H2Bub1 occupancy. These correlated with changes in the expression of genes associated with myelination and lipid metabolism. We determined the genome-wide H2Bub1 occupancy in sciatic nerves of 14-day old control mice (ctrl; carrying floxed Rnf40 alleles) and mice with a Schwann cell-specific Rnf40 deletion (cko; carrying Rnf40 alleles in combination with a Dhh::Cre transgene) using the Illumina HiSeq 2500 platform.