Differential CTCF binding in motor neurons and lymphocytes

Transcriptional regulation of protein-coding genes is a primary control mechanism of cellular function. Similarities in regulation of expression for select genes between lymphocytes and neurons have led to proposals that such genes may be useful biomarkers for some neurological disorders that can be monitored via patient lymphocyte populations. Examination of shared molecular mechanisms underlying neurogenesis and lymphocyte differentiation may give help to identify relevant pathways and suggest additional biomarkers in lymphocytes that are relevant to neurological disorders. In this study, we analysed similarities and conserved regions in several genes regulated by CCCTC-binding factor (CTCF) during lymphocyte and neuronal developmental stages. We performed epigenetic analysis of CTCF binding Trak1, Gabpa, Gabpb1, Gabpb2, Gfi1, Gfi1b gene loci at T and B lymphocytes at different developmental stages, as well as in neural progenitor cells and motor neurons. Common and shared CTCF binding events at Trak1 gene suggest additional transcriptional regulatory factors that control Trak1 gene expression levels differ in neurons and lymphocytes. Gabpb1 gene 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. In contrast, while Gfi1a gene is phylogenetically well-conserved and CTCF sites are occupied in lymphocytes, there are no CTCF binding occupied in neurons and neural progenitor cells. Low expression levels of Gfi1s in neurons indicate that regulation of this gene is CTCF-independent in neurons. 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, although lineage specific transcriptional regulators that play a role in their different expression levels still need to be identified. The partial overlap in CTCF regulatory sites for some genes in neurons and lymphocytes suggest that there may be markers that can exhibit parallel changes in these cells and serve as biomarkers.