Identification of neuronal target genes for CCAAT/enhancer binding proteins.
CCAAT/Enhancer Binding Proteins (C/EBPs) play pivotal roles in the development and plasticity of the nervous system. Identification of the physiological targets of C/EBPs (C/EBP target genes) should therefore provide insight into the underlying biology of these processes. We used unbiased genome-wide mapping to identify 115 C/EBPbeta target genes in PC12 cells that include transcription factors, neurotransmitter receptors, ion channels, protein kinases and synaptic vesicle proteins. C/EBPbeta binding sites were located primarily within introns, suggesting novel regulatory functions, and were associated with binding sites for other developmentally important transcription factors. Experiments using dominant negatives showed C/EBPbeta to repress transcription of a subset of target genes. Target genes in rat brain were subsequently found to preferentially bind C/EBPalpha, beta and delta. Analysis of the hippocampal transcriptome of C/EBPbeta knockout mice revealed dysregulation of a high percentage of transcripts identified as C/EBP target genes. These results support the hypothesis that C/EBPs play non-redundant roles in the brain.
Kfoury
Najla
N
Center for Molecular Medicine and Genetics, Wayne State University School of Medicine, Detroit, MI, USA.
Kapatos
Gregory
G
D000818:Animals; D001665:Binding Sites; D001921:Brain / Q000166:cytology / Q000378:metabolism; D022762:CCAAT-Enhancer-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D047369:Chromatin Immunoprecipitation; D000242:Cyclic AMP / Q000378:metabolism; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D053263:Gene Regulatory Networks; D006801:Humans; D051379:Mice; D018345:Mice, Knockout; D008969:Molecular Sequence Data; D009474:Neurons / Q000502:physiology*; D016716:PC12 Cells; D020033:Protein Isoforms / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D015203:Reproducibility of Results
D022762:CCAAT-Enhancer-Binding Proteins; D020033:Protein Isoforms; D000242:Cyclic AMP