Analysis of the Epigenetic State of the Dm Element within the Igκ Locus in Pre-B Cells

Background: The Igκ locus undergoes multiple molecular processes during B cell development, including V(D)J recombination and epigenetic regulation, which are influenced by cis-regulatory regions within the locus. A novel cis-regulatory region, termed the Dm element, has been identified. It functions in coordination with the 3′Eκ and Ed enhancers and has been implicated in Igκ demethylation and somatic hypermutations (SHM). The Dm element is characterized by a high density of CpG dinucleotides, a hallmark of region subject to DNA methylation. Our previous work demonstrated that RAG2, but not RAG1, contributes to the Igκ locus demethylation. However, whether RAG proteins influence the epigenetic state of the Dm element remains unknown. Methods: Here, we investigated the epigenetic state of the Dm element using bisulfite sequencing and chromatin immunoprecipitation (ChIP). Results: We found that the Dm element was hypermethylated in pre-B cells but partially demethylated in splenic B cells. Furthermore, it was marked by active histone modifications, including H3K27Ac and H3K9Ac, and was bound by B cell-specific transcription factor Pax5 in pre-B cells. Conclusion: Our findings provide evidence that the Dm element undergoes DNA methylation remodeling in mature B cells, potentially contributing to Igκ allelic expression.