Ordered spacing of pluripotency transcription factors, binding to the HERV-H 5′ LTR in human ES cells. (A) Association strength (F score) of NANOG, OCT4 and SOX2 binding sites with the 50 most highly expressed HERV-H proviruses (accounting for 80% of total HERV-H expression), as a function of distance from the HERV-H transcription start site (TSS). Maxima in F score indicate the distance of greatest association. (B) Average distance of NANOG (red), OCT4 (blue) and SOX2 (green) to HERV-H TSS is shown schematically. As expected from a uniform distribution model, the average distance is half of the distance between maximal association and TSS. (C) Chromosome Projection Mandala combining NANOG, OCT4 and SOX2 with respect to 50 HERV-H proviruses. The three embryonic transcription factors bind with the same order (NANOG-OCT4-SOX2) to the promoter region of the most expressed HERV-Hs.