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.