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ZFP982 confers mouse embryonic stem cell characteristics by regulating expression of Nanog, Zfp42 and Dppa3

We here used multi-omics analyses to identify and characterize zinc finger protein 982 (Zfp982) that confers stemness characteristics by regulating expression of Nanog, Zfp42 and Dppa3 in mouse embryonic stem cells (mESC). Network-based expression analyses comparing the transcriptional profiles of mESC and differentiated cells revealed high expression of Zfp982 in stem cells. Moreover, Zfp982 showed transcriptional overlap with Yap1, the major co-activator of the Hippo pathway. Quantitative proteomics and co-immunoprecipitation revealed interaction of ZFP982 with YAP1. ZFP982 used a GCAGAGKC motif to bind to chromatin, for example near the stemness conferring genes Nanog, Zfp42 and Dppa3 as shown by ChIP-seq. Loss-of-function experiments in mESC established that expression of Zfp982 is necessary to maintain stem cell characteristics. Zfp982 expression decreased with progressive differentiation, and knockdown of Zfp982 resulted in neural differentiation of mESC. ZFP982 localized to the nucleus in mESC and translocated to the cytoplasm upon neuronal differentiation. Similarly, YAP1 localized to the cytoplasm upon differentiation, but in mESC YAP1 was present in the nucleus and cytoplasm. Graphical Abstract ZFP982 is a regulator of stemness of mouse embryonic stem cells and acts as transcription factor by activating expression of stem cell genes including Nanog, Dppa3 and Zfp42. Highlights Zfp982 is a new mouse stem cell defining marker gene. Zfp982 is co-expressed with Yap1 and stem cell marker genes in mESC. ZFP982 binds to DNA and induces expression of master genes of stemness in mESC. Expression of Zfp982 gene prevents neural differentiation and maintains stem cell characteristics. ZFP982 and YAP1 interact in mESC and translocate to the cytoplasm upon neural differentiation.