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Spacer sequences separating transcription factor binding motifs set enhancer quality and strength

Marion Guéroult-Bellone, Kazuhiro R. Nitta, Willi Kari, Edwin Jacox, Rémy Beulé Dauzat, View ORCID ProfileRenaud Vincentelli, Carine Diarra, Ute Rothbächer, Christelle Dantec, View ORCID ProfileChristian Cambillau, Jacques Piette, View ORCID ProfilePatrick Lemaire
doi: https://doi.org/10.1101/098830
Marion Guéroult-Bellone
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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Kazuhiro R. Nitta
2Institut de Biologie du Dévelopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ. - Case 907, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
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Willi Kari
2Institut de Biologie du Dévelopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ. - Case 907, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
3Current address: Department of Evolution and Developmental Biology, Zoological Institute, University Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
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Edwin Jacox
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
2Institut de Biologie du Dévelopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ. - Case 907, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
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Rémy Beulé Dauzat
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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Renaud Vincentelli
4Architecture et Fonction des Macromolécules Biologiques-AFMB - UMR7257 CNRS - Aix-Marseille Univ. - Case 932, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
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Carine Diarra
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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Ute Rothbächer
2Institut de Biologie du Dévelopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ. - Case 907, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
3Current address: Department of Evolution and Developmental Biology, Zoological Institute, University Innsbruck, Technikerstrasse 25, A-6020 Innsbruck, Austria.
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Christelle Dantec
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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Christian Cambillau
4Architecture et Fonction des Macromolécules Biologiques-AFMB - UMR7257 CNRS - Aix-Marseille Univ. - Case 932, 163 Avenue de Luminy 13288 Marseille CEDEX 09 FRANCE
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Jacques Piette
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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Patrick Lemaire
1Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Université de Montpellier, 1919 route de Mende, 34293 Montpellier, France
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ABSTRACT

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.

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Posted January 06, 2017.
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Spacer sequences separating transcription factor binding motifs set enhancer quality and strength
Marion Guéroult-Bellone, Kazuhiro R. Nitta, Willi Kari, Edwin Jacox, Rémy Beulé Dauzat, Renaud Vincentelli, Carine Diarra, Ute Rothbächer, Christelle Dantec, Christian Cambillau, Jacques Piette, Patrick Lemaire
bioRxiv 098830; doi: https://doi.org/10.1101/098830
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Spacer sequences separating transcription factor binding motifs set enhancer quality and strength
Marion Guéroult-Bellone, Kazuhiro R. Nitta, Willi Kari, Edwin Jacox, Rémy Beulé Dauzat, Renaud Vincentelli, Carine Diarra, Ute Rothbächer, Christelle Dantec, Christian Cambillau, Jacques Piette, Patrick Lemaire
bioRxiv 098830; doi: https://doi.org/10.1101/098830

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