TY - JOUR T1 - Spacer sequences separating transcription factor binding motifs set enhancer quality and strength JF - bioRxiv DO - 10.1101/098830 SP - 098830 AU - Marion Guéroult-Bellone AU - Kazuhiro R. Nitta AU - Willi Kari AU - Edwin Jacox AU - Rémy Beulé Dauzat AU - Renaud Vincentelli AU - Carine Diarra AU - Ute Rothbächer AU - Christelle Dantec AU - Christian Cambillau AU - Jacques Piette AU - Patrick Lemaire Y1 - 2017/01/01 UR - http://biorxiv.org/content/early/2017/01/06/098830.abstract N2 - Only a minority of the many genomic clusters of transcription factor binding motifs (TFBM) act as transcriptional enhancers. To identify determinants of enhancer activity, we randomized the spacer sequences separating the ETS and GATA sites of the early neural enhancer of the tunicate Ciona intestinalis Otx gene. We show that spacer sequence randomization affects the level of activity of the enhancer, in part through distal effects on the affinity of the transcription factors for their binding sites. A possible mechanism is suggested by the observation that the shape of the DNA helix within the TFBM can be affected by mutation of flanking bases that modulate transcription factor affinity. Strikingly, dormant genomic clusters of ETS and GATA sites are awakened by most instances of spacer randomization, suggesting that the sequence of naturally-occurring spacers ensures the dormancy of a majority of the large reservoir of TFBM clusters present in a metazoan genome. ER -