Genome-wide dissection of posttranscriptional and posttranslational interactions

Transcriptional interactions in the cell are modulated by a variety of posttranscriptional and posttranslational mechanisms that make them highly dependent on the molecular context of the specific cell. These include, among others, microRNA-mediated control of transcription factor (TF) mRNA translation and degradation, transcription factor activation by phosphorylation and acetylation, formation of active complexes with one or more cofactors, and mRNA/protein degradation and stabilization processes. Thus, the ability of a transcription factor to regulate its targets depends on a variety of genetic and epigenetic mechanisms, resulting in highly context-dependent regulatory networks. In this chapter, we introduce a step-by-step guide on how to use the MINDy systems biology algorithm (Modulator Inference by Network Dynamics) that we recently developed, for the genome-wide, context-specific identification of posttranscriptional and posttranslational modulators of transcription factor activity.