Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

Genome-wide identification of Bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling.

Blog Article

B-cell leukemia/lymphoma 11B (Bcl11b) is a transcription factor showing predominant expression in the striatum.To date, there are no known gene targets of Bcl11b in the nervous system.Here, we 5.5/5RV define targets for Bcl11b in striatal cells by performing chromatin immunoprecipitation followed by high-throughput sequencing (ChIP-seq) in combination with genome-wide expression profiling.Transcriptome-wide analysis revealed that 694 genes were significantly altered in striatal cells over-expressing Bcl11b, including genes showing striatal-enriched expression similar to Bcl11b.

ChIP-seq analysis demonstrated that Bcl11b bound a mixture of coding and non-coding sequences that were within 10 kb of the transcription start site of an annotated gene.Integrating all ChIP-seq hits with the microarray expression data, 248 direct targets of Bcl11b were identified.Functional analysis on the integrated gene target list identified several zinc-finger encoding genes as Bcl11b targets, and further revealed a significant association of Bcl11b to brain-derived neurotrophic Plush Toy factor/neurotrophin signaling.Analysis of ChIP-seq binding regions revealed significant consensus DNA binding motifs for Bcl11b.

These data implicate Bcl11b as a novel regulator of the BDNF signaling pathway, which is disrupted in many neurological disorders.Specific targeting of the Bcl11b-DNA interaction could represent a novel therapeutic approach to lowering BDNF signaling specifically in striatal cells.