Abstract
Transcriptional enhancers in the cell nuclei typically interact with the target promoters in cis over long stretches of chromatin, but the mechanism of this communication remains unknown. Previously we have developed a defined in vitro system for quantitative analysis of the rate of distant enhancer-promoter communication (EPC) and have shown that the chromatin fibers maintain efficient distant EPC in cis. Here we investigate the roles of linker histone H1 and HMGN5 protein in EPC. A considerable negative effect of histone H1 on EPC depending on its C- and N-tails was shown. Protein HMGN5 that affects chromatin compaction and is associated with active chromatin counteracts EPC inhibition by H1. The data suggest that the efficiency of the interaction between the enhancer and the promoter depends on the structure and dynamics of the chromatin fiber localized between them and can be regulated by proteins associated with chromatin.
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ACKNOWLEDGMENTS
We thank T. Richmond (ETH Zürich, Institute of Molecular Biology and Biophysics, Zürich, Switzerland) for the plasmid containing 601177 × 12 nucleosome positioning sequences and S. Dimitrov (Université Grenoble Alpes, CNRS UMR 5309, INSERM U1209, Institute for Advanced Biosciences (IAB), Site Santé—Allée des Alpes, France) for intact and mutant histone H1.
Funding
This work was supported by NIH RO1GM119398 and R21CA220151 to Studitsky V.M., RO1GM34809 to W.K. Olson and by Russian Science Foundation (grant 14-24-00031). Polikanov Y.S. work was sponsored by Illinois State start-up funds, USA. Work of Y.V. Postnikov was sponsored by National Institutes of Health, National Cancer Institute, USA.
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Authors E.V. Nizovtseva and Y.S. Polikanov contributed equally.
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Nizovtseva, E.V., Polikanov, Y.S., Kulaeva, O.I. et al. Opposite Effects of Histone H1 and HMGN5 Protein on Distant Interactions in Chromatin. Mol Biol 53, 912–921 (2019). https://doi.org/10.1134/S002689331906013X
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DOI: https://doi.org/10.1134/S002689331906013X
Keywords:
- chromatin
- enhancer-promotor communication
- transcription in vitro
- Н1
- HMGN5