The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise
- Kin Chung Lam1,6,
- Ho-Ryun Chung2,3,6,
- Giuseppe Semplicio1,
- Shantanu S. Iyer1,4,5,
- Aline Gaub1,5,
- Vivek Bhardwaj1,
- Herbert Holz1,
- Plamen Georgiev1 and
- Asifa Akhtar1
- 1Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, 79108 Freiburg, Germany;
- 2Otto-Warburg-Laboratory, Epigenomics, Max Planck Institute for Molecular Genetics, 14195 Berlin, Germany;
- 3Institute for Medical Bioinformatics and Biostatistics, Philipps-Universität Marburg, 35037 Marburg, Germany;
- 4Spemann Graduate School of Biology and Medicine (SGBM), University of Freiburg, 79108 Freiburg, Germany;
- 5Faculty of Biology, University of Freiburg, 79108 Freiburg, Germany
- Corresponding author: akhtar{at}ie-freiburg.mpg.de
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↵6 These authors contributed equally to this work.
Abstract
Nucleosomal organization at gene promoters is critical for transcription, with a nucleosome-depleted region (NDR) at transcription start sites (TSSs) being required for transcription initiation. How NDRs and the precise positioning of the +1 nucleosomes are maintained on active genes remains unclear. Here, we report that the Drosophila nonspecific lethal (NSL) complex is necessary to maintain this stereotypical nucleosomal organization at promoters. Upon NSL1 depletion, nucleosomes invade the NDRs at TSSs of NSL-bound genes. NSL complex member NSL3 binds to TATA-less promoters in a sequence-dependent manner. The NSL complex interacts with the NURF chromatin remodeling complex and is necessary and sufficient to recruit NURF to target promoters. Not only is the NSL complex essential for transcription, but it is required for accurate TSS selection for genes with multiple TSSs. Furthermore, loss of the NSL complex leads to an increase in transcriptional noise. Thus, the NSL complex establishes a canonical nucleosomal organization that enables transcription and determines TSS fidelity.
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Footnotes
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Supplemental material is available for this article.
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Article published online ahead of print. Article and publication date are online at http://www.genesdev.org/cgi/doi/10.1101/gad.321489.118.
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Freely available online through the Genes & Development Open Access option.
- Received October 7, 2018.
- Accepted January 11, 2019.
This article, published in Genes & Development, is available under a Creative Commons License (Attribution 4.0 International), as described at http://creativecommons.org/licenses/by/4.0/.
