genome-wide identification of bcl11b gene targets reveals role in brain-derived neurotrophic factor signaling全基因组bcl11b基因的识别目标在脑源性神经营养因子的信号显示的作用.pdfVIP

Genome-Wide Identification of Bcl11b Gene Targets Reveals Role in Brain-Derived Neurotrophic Factor Signaling 1 2 3 3 2 1 Bin Tang , Pietro Di Lena , Lana Schaffer , Steven R. Head , Pierre Baldi , Elizabeth A. Thomas * 1 Department of Molecular Biology, The Scripps Research Institute, La Jolla, California, United States of America, 2 Department of Computer Science and Institute for Genomics and Bioinformatics, University of California, Irvine, Irvine, California, United States of America, 3 Department of Shared Research Services, The Scripps Research Institute, La Jolla, California, United States of America Abstract 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 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 brai