IN SILICO INSIGHT INTO THE REGULATORY NODES OF CELL FATE

Abstract

Stem cells are capable of self-renewal or differentiation. The fate of stem cells is determined by specific molecular factors such as chromatin modifications, endogenous retroviral elements (ERVs) and transcriptions factors. However, the mechanisms by which the interplay of these factors governs cell fate remain largely elusive. Genome-wide siRNA screen coupled with computational analyses revealed histone chaperone Chaf1a to regulate ERV silencing via H3K9me3-dependent or independent manner. Additionally, histone variant H3.3, was shown to preserve cell lineages by triggering the activation of specific genes thereby acting as a roadblock for cell fate switching. Moreover, single-cell RNA-Seq and Assay for Transposase-Accessible Chromatin (ATAC)-Seq demonstrated that the deactivation of enhancers bound by FRA1 resulted in an intermediate state of cells that can be reprogrammed into new cell types. Taken together, the determination of cell fate was found to be supervised by an intricate network of regulatory nodes.