Spacer sequences separating transcription factor binding motifs set enhancer quality and strength
Spacer sequences separating transcription factor binding motifs set enhancer quality and strength
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.
Lemaire Patrick、Gu¨|roult-Bellone Marion、Kari Willi、Beul¨| Dauzat R¨|my、Vincentelli Renaud、Rothb?cher Ute、Cambillau Christian、Nitta Kazuhiro R.、Dantec Christelle、Diarra Carine、Jacox Edwin、Piette Jacques
Centre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de MontpellierCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de MontpellierInstitut de Biologie du D¨|velopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ||Department of Evolution and Developmental Biology, Zoological Institute, University InnsbruckCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de MontpellierArchitecture et Fonction des Macromol¨|cules Biologiques-AFMB - UMR7257 CNRS - Aix-Marseille UnivInstitut de Biologie du D¨|velopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille Univ||Department of Evolution and Developmental Biology, Zoological Institute, University InnsbruckArchitecture et Fonction des Macromol¨|cules Biologiques-AFMB - UMR7257 CNRS - Aix-Marseille UnivInstitut de Biologie du D¨|velopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille UnivCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de MontpellierCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de MontpellierCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de Montpellier||Institut de Biologie du D¨|velopment de Marseille- IBDM, UMR7288 CNRS - Aix-Marseille UnivCentre de Recherche en Biologie cellulaire de Montpellier, UMR 5237, CNRS-Universit¨| de Montpellier
分子生物学遗传学细胞生物学
Ciona intestinalisgene regulationdevelopmentenhancertranscription factorDNA shapeEtsGataOtxascidiantranscription factor affinity
Lemaire Patrick,Gu¨|roult-Bellone Marion,Kari Willi,Beul¨| Dauzat R¨|my,Vincentelli Renaud,Rothb?cher Ute,Cambillau Christian,Nitta Kazuhiro R.,Dantec Christelle,Diarra Carine,Jacox Edwin,Piette Jacques.Spacer sequences separating transcription factor binding motifs set enhancer quality and strength[EB/OL].(2025-03-28)[2025-05-10].https://www.biorxiv.org/content/10.1101/098830.点此复制
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