Abstract
The pluripotent state is not solely governed by the action of the core transcription factors OCT4, SOX2, and NANOG, but also by a series of co‐transcriptional and post‐transcriptional events, including alternative splicing (AS) and the interaction of RNA‐binding proteins (RBPs) with defined subpopulations of RNAs. Zinc Finger Protein 207 (ZFP207) is an essential transcription factor for mammalian embryonic development. Here, we employ multiple functional analyses to characterize its role in mouse embryonic stem cells (ESCs). We find that ZFP207 plays a pivotal role in ESC maintenance, and silencing of Zfp207 leads to severe neuroectodermal differentiation defects. In striking contrast to human ESCs, mouse ZFP207 does not transcriptionally regulate neuronal and stem cell‐related genes but exerts its effects by controlling AS networks and by acting as an RBP. Our study expands the role of ZFP207 in maintaining ESC identity, and underscores the functional versatility of ZFP207 in regulating neural fate commitment.
Highlights
Mouse embryonic stem cells (ESCs) are derived from the inner cell mass of the pre-implantation blastocyst
Real-time quantitative reverse transcription PCR (RT-qPCR) revealed that Zfp207 was significantly enriched in ESCs compared to differentiated cells (Fig 1A and B), and its expression levels gradually decreased along the course of differentiation, correlating with the decrease of Zinc Finger Protein 207 (ZFP207) and OCT4 protein levels (Fig 1C and D)
Depletion of Zfp207 led to a reduced proliferation capacity compared to ESCs transduced with scrambled short-hairpin RNAs (shRNAs), to a lesser degree in KD1 than in KD2 ESCs (Fig 1G; 1.3 and 2-fold, respectively)
Summary
Mouse embryonic stem cells (ESCs) are derived from the inner cell mass of the pre-implantation blastocyst. Zinc finger-containing proteins (ZFN or ZFP for human or mouse, respectively) are among the largest family of proteins, commonly containing a minimum of one zinc-finger (ZnF) domain, which recognizes DNA sequences with high affinity. This family of transcription factors plays important roles in a variety of cellular processes including development, cellular differentiation, metabolism and oncogenesis (Cassandri et al, 2017). It associates with Bub and with spindle microtubules to regulate chromosome alignment (Jiang et al, 2014, 2015; Toledo et al, 2014). Both ZNF207 and Bub interact with the spliceosome and are required for interphase RNA splicing (Wan et al, 2015), yet its specific molecular role remains elusive
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