Differential CTCF binding in motor neurons and lymphocytes

Abstract

Background: Diversity is critical to lymphocyte roles in the immune system and to neurons, which form complex network structures in the brain. Emerging evidence suggests that an increasing number of molecules associated with the immune system are also expressed in various central nervous system (CNS) regions and play crucial roles in brain development. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may clarify relevant pathways, and suggests additional biomarkers in lymphocytes for neurological disorders. These results can contribute to find biomarkers that can be monitored through patient lymphocyte populations. Methods: We analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analyses of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci in T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Results: Common and shared CTCF binding events at Trak1 suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 includes a common CTCF binding site shared with neurons and lymphocytes. Correlation of CTCF binding analysis and gene expression profile suggests that CTCF binding plays a role in epigenetic regulation of Gabpb1 gene. While Gfi1a is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Although Gfi1b is highly homologous to Gfi1, differences in expression levels suggest that Gfi1b is critical for both lymphogenesis and neurogenesis. Neurons and lymphocytes have multiple common CTCF binding sites in the Gfi1b gene. Conclusions: The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggests that there may be markers which can exhibit parallel changes in these cells and serve as biomarkers.