A quantitative model of transcription regulation reveals the role of non-conserved enhancers

We identify sites of combinatorial control by performing high throughput ChIP experiments on p300, CREB-binding protein (CBP), the deacetylase SIRT1 and on multiple DNA-binding transcription factors in three different tissues. We present a quantitative model of transcriptional regulation that reveals the contribution of each binding site to tissue-specific gene expression in several mouse cell types. Binding to both evolutionarily conserved and non-conserved sequences is found to contribute significantly to transcriptional regulation. We demonstrate that binding location strongly predicts the expression level of nearby genes. Liver hepatocytes and cerebellum tissue were harvested from male C57BL/6J mice. RNA was extracted and hybridized to Affymetrix arrays. Examination of transcriptional regulator binding in three mouse tissues by ChIP-IP using tiling arrays. Examination of CBP binding in mouse liver and cerebellum by ChIP-seq.