Role of TAF5L and TAF6L in controlling the mouse ESC state [ChIP-seq]

Self-renewal and pluripotency of the embryonic stem cell (ESC) state is established and maintained by multiple regulatory networks that comprise transcription factors and epigenetic regulators. Although many studies have been performed, the function of epigenetic regulators in these networks is incompletely defined. We conducted a CRISPR-Cas9 mediated loss-of-function genetic screen to target 323 epigenetic and ESC-specific transcription factor genes. This screen identified two new epigenetic regulators—TAF5L and TAF6L—with high confidence for the mouse ESC state. TAF5L and TAF6L are also essential for the efficient somatic reprogramming. In-depth analyses demonstrate that TAF5L and TAF6L belong to and establish a regulatory circuitry with MYC and CORE networks. Moreover, detailed molecular studies reveal TAF5L and TAF6L predominantly regulate their target genes through the c-MYC and MYC regulatory network to control self-renewal of mouse ESCs. Our findings illuminate the multi-layered regulatory networks of TAF5L and TAF6L for gene regulation to maintain the ESC state.