Genome-wide IMPDH profiling in Drosophila larvae and S2 cells by ChIP-chip.. Drosophila melanogaster

Division of labor is a central feature of cellular organization. Consequently, gene regulation and intermediary metabolism are generally believed to be conducted by strictly separate classes of proteins. Here, we show that inosine monophosphate dehydrogenase (IMPDH), the central enzyme in guanine nucleotide biosynthesis, moonlights as a gene-specific transcription factor. Nuclear exclusion during S phase coordinates IMPDH’s transcriptional activities with the cell cycle. IMPDH represses target gene expression, including the histone genes. Unexpectedly, genomic IMPDH loci have the propensity to unwind. Genome-wide profiling and in vitro experiments revealed that IMPDH binds sequence-specifically to single stranded C/T-rich DNA elements. Thus, a classic biosynthetic enzyme can act as a DNA-binding transcription factor, suggestive of a more reciprocal and intimate relationship between metabolism and gene expression than commonly assumed. Overall design: Genome-wide IMPDH profiling in Drosophila S2 cells by ChIP-chip. The supplementary bed file 'S2_IMPDH_regions.bed' contains high-quality binding sites for IMPDH obtained by intersecting the sets of significant ChIP-chip peaks from 3 biological replicates. Genome-wide IMPDH profiling in Drosophila larvae by ChIP-chip The supplementary bed file larvae_IMPDH_regions.bed contains high quality binding sites for IMPDH obtained by intersecting the sets of significant ChIP-chip peaks from 4 biological replicates.