Abstract In mammals, a number of distinct mechanisms govern the regulation of gene expression. MicroRNAs are ~21nt RNAs that repress mRNAs by forming a complex with Argonaute proteins and binding to the mRNA 3’UTR. The individual knockout of several RNAi genes, involved in miRNAs biogenesis, leads to a large number of misregulated genes. Nevertheless, only a small number of misregulated genes were commonly observed in all RNAi mutant mESCs. Indeed, the different deletion mutants show a very different differential gene expression patterns, raising the question of which specific mechanisms are responsible for the large number of misregulated genes in individual mutant cell lines.
In order to identify the leading causes, I integrated several OMICs data obtained from these RNAi mutant mESCs, as well as publicly available datasets. I observed that chromatin-associated regulation mechanisms like histone modifications are perturbed and contribute greatly to the observed deregulation.
Furthermore, I present an attempt to integrate descriptive data for chromatin opening, histone modifications, transcription factors and miRNA-mediated regulation to gain an understanding of what contributes most to the deregulation of genes in individual microRNA-depleted cells.