Using genomics to understand the gene selectivity of steroid hormone receptors

2014-09-16The remodelling of chromatin and regulated assembly or disassembly of active transcription complexes by glucocorticoid receptor and other DNA-binding transcription factors is mediated and modulated by several hundred transcriptional coregulator proteins. Previous studies focusing on single coregulators demonstrated that each coregulator is required for regulation of only a subset of all the genes regulated by a steroid hormone. I analyze gene-specific patterns of coregulators and find that depleting specific coregulators corresponds to changes in physiological pathways. I find that different coregulators modulate the pathway-specificity of hormone action and thus providing a mechanism for fine tuning of the hormone response. ❧ ChIP-seq, a technique that is used to determine genome-wide protein binding, is used to understand the dynamics of transcription factor binding. Recently, interest in comparing protein binding between different biological conditions has increased, accompanied by an increase in new software for data analysis. Approaches for differential transcription factor binding utilize methods developed for RNA-seq. I apply these new software tools to a variety of data sets from the ENCODE project to illustrate the impact of data processing pipelines under different biological conditions. I present best practice guidelines for transcription factor binding analysis and provide points for discussion between biologists who perform the ChIP-seq experiment and bioinformaticians who analyze the data