INVESTIGATING THE ROLES OF NPAC AND ZFP553 IN MOUSE ES CELL IDENTITY AND REPROGRAMMING

Abstract

Embryonic stem cells (ESCs) are able to replicate themselves indefinitely and possess the potential to differentiate into many distinct cell types. The unique ESC identity is delicately governed by a complex transcriptional network in collaboration with epigenetic regulation. Therefore, it is important to understand both genetic and epigenetic mechanisms of pluripotency maintenance in ESC identity and somatic cell reprogramming. In this study, we identified one transcription factor, Zfp553 and an epigenetic factor, Npac as novel pluripotency factors. Zfp553 regulates key pluripotency genes Nanog and Pou5f1 and is required for pluripotency maintenance. We also showed that Zfp553 is essential for somatic cell reprogramming. Moreover, we discovered that Npac can regulate pluripotency by activating pluripotency related genes and repressing developmental genes. Interestingly, Npac is co-localized with histone H3K36Me3 in mouse ES genome. In addition, we showed that Npac could be involved in transcriptional elongation of some pluripotency genes. Together, these results provide new insights into pluripotency regulation by both genetic and epigenetic mechanisms.