A distinct isoform of ZNF207 controls self-renewal and pluripotency of human embryonic stem cells

Fang Fang (), Ninuo Xia, Benjamin Angulo, Joseph Carey, Zackery Cady, Jens Durruthy-Durruthy, Theo Bennett, Vittorio Sebastiano and Renee A. Reijo Pera
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Fang Fang: Montana State University
Ninuo Xia: Montana State University
Benjamin Angulo: Montana State University
Joseph Carey: Montana State University
Zackery Cady: Montana State University
Jens Durruthy-Durruthy: Stanford University School of Medicine
Theo Bennett: Montana State University
Vittorio Sebastiano: Stanford University School of Medicine
Renee A. Reijo Pera: Montana State University

Nature Communications, 2018, vol. 9, issue 1, 1-14

Abstract: Abstract Self-renewal and pluripotency in human embryonic stem cells (hESCs) depends upon the function of a remarkably small number of master transcription factors (TFs) that include OCT4, SOX2, and NANOG. Endogenous factors that regulate and maintain the expression of master TFs in hESCs remain largely unknown and/or uncharacterized. Here, we use a genome-wide, proteomics approach to identify proteins associated with the OCT4 enhancer. We identify known OCT4 regulators, plus a subset of potential regulators including a zinc finger protein, ZNF207, that plays diverse roles during development. In hESCs, ZNF207 partners with master pluripotency TFs to govern self-renewal and pluripotency while simultaneously controlling commitment of cells towards ectoderm through direct regulation of neuronal TFs, including OTX2. The distinct roles of ZNF207 during differentiation occur via isoform switching. Thus, a distinct isoform of ZNF207 functions in hESCs at the nexus that balances pluripotency and differentiation to ectoderm.

Date: 2018
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DOI: 10.1038/s41467-018-06908-5

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