Having demonstrated a functional role for lincRNAs in ESCs, we sought to integrate the lincRNAs into the molecular circuitry controlling the pluripotent state. First, we explored how lincRNA expression is regulated in ESCs. Toward this end, we utilized published genome-wide maps of 9 pluripotency-associated transcription factors (TFs)16,38 and determined whether they bind to the promoters of lincRNA genes. Of the 226 lincRNA promoters ~75% are bound by at least one of 9 pluripotency-associated TFs (including Oct4, Sox2, Nanog, cMyc, nMyc, Klf4, Zfx, Smad, and Tcf3) with a median of 3 factors bound to each promoter (Figure 4a, Supplemental Figure 11, Supplemental Table 14), comparable to the proportion reported for protein-coding genes16. Interestingly, the 3 core factors (Oct4, Sox2, and Nanog) bind to the promoters of ~12% of all ESC lincRNAs and ~50% of lincRNAs involved in the regulation of the pluripotent state.
