The interaction landscape between transcription factors and the nucleosome
The interaction landscape between transcription factors and the nucleosome
Nucleosomes cover most of the genome and are thought to be displaced by transcription factors (TFs) in regions that direct gene expression. However, the modes of interaction between TFs and nucleosomal DNA remain largely unknown. Here, we use nucleosome consecutive affinity-purification systematic evolution of ligands by exponential enrichment (NCAP-SELEX) to systematically explore interactions between the nucleosome and 220 TFs representing diverse structural families. Consistently with earlier observations, we find that the vast majority of TFs have less access to nucleosomal DNA than to free DNA. The motifs recovered from TFs bound to nucleosomal and free DNA are generally similar; however, steric hindrance and scaffolding by the nucleosome result in specific positioning and orientation of the motifs. Many TFs preferentially bind close to the end of nucleosomal DNA, or to periodic positions at its solvent-exposed side. TFs often also bind nucleosomal DNA in a particular orientation, because the nucleosome breaks the local rotational symmetry of DNA. Some TFs also specifically interact with DNA located at the dyad position where only one DNA gyre is wound, whereas other TFs prefer sites spanning two DNA gyres and bind specifically to each of them. Our work reveals striking differences in TF binding to free and nucleosomal DNA, and uncovers a rich interaction landscape between the TFs and the nucleosome.
Farnung Lucas、Sahu Biswajyoti、Yin Yimeng、Wei Bei、Cramer Patrick、Zhu Fangjie、Kaasinen Eevi、Dodonova Svetlana、Taipale Jussi
Max Planck Institute for Biophysical Chemistry, Department of Molecular BiologyDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetMax Planck Institute for Biophysical Chemistry, Department of Molecular Biology||Center for Innovative Medicine and Science for Life Laboratory, Department of Biosciences and Nutrition, Karolinska InstitutetDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska InstitutetMax Planck Institute for Biophysical Chemistry, Department of Molecular BiologyDivision of Functional Genomics and Systems Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet||Genome-Scale Biology Program
分子生物学遗传学生物物理学
Farnung Lucas,Sahu Biswajyoti,Yin Yimeng,Wei Bei,Cramer Patrick,Zhu Fangjie,Kaasinen Eevi,Dodonova Svetlana,Taipale Jussi.The interaction landscape between transcription factors and the nucleosome[EB/OL].(2025-03-28)[2025-05-23].https://www.biorxiv.org/content/10.1101/240598.点此复制
评论