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The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise

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Lam,  Kin-Chung
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Semplicio,  Giuseppe
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Iyer,  Shantanu S.
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Gaub,  Aline
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

Bhardwaj,  Vivek
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons198899

Holz,  Herbert
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons198893

Georgiev,  Plamen
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

/persons/resource/persons198888

Akhtar,  Asifa
Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society;

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Citation

Lam, K.-C., Chung, H.-R., Semplicio, G., Iyer, S. S., Gaub, A., Bhardwaj, V., et al. (2019). The NSL complex-mediated nucleosome landscape is required to maintain transcription fidelity and suppression of transcription noise. Genes and Development, 33, 453-465. doi:10.1101/gad.321489.118.


Cite as: http://hdl.handle.net/21.11116/0000-0005-1CBE-7
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.