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  Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex

Dias, J., Van Nguyen, N., Georgiev, P., Gaub, A., Brettschneider, J., Cusack, S., et al. (2014). Structural analysis of the KANSL1/WDR5/KANSL2 complex reveals that WDR5 is required for efficient assembly and chromatin targeting of the NSL complex. Genes and Development, 28, 929-942.

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 Creators:
Dias, Jorge1, Author
Van Nguyen, Nhuong2, Author              
Georgiev, Plamen2, Author              
Gaub, Aline3, Author
Brettschneider, Janine1, Author
Cusack, Stephan1, Author
Kadlec, Jan1, Author
Akhtar, Asifa2, Author              
Affiliations:
1External Organizations, ou_persistent22              
2Department of Chromatin Regulation, Max Planck Institute of Immunobiology and Epigenetics, Max Planck Society, ou_2243643              
3Max Planck Society, ou_persistent13              

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Free keywords: chromatin; epigenetics; histone acetylation
 Abstract: The subunits of the nonspecific lethal (NSL) complex, which include the histone acetyltransferase MOF (males absent on the first), play important roles in various cellular functions, including transcription regulation and stem cell identity maintenance and reprogramming, and are frequently misregulated in disease. Here, we provide the first biochemical and structural insights into the molecular architecture of this large multiprotein assembly. We identified several direct interactions within the complex and show that KANSL1 acts as a scaffold protein interacting with four other subunits, including WDR5, which in turn binds KANSL2. Structural analysis of the KANSL1/WDR5/KANSL2 subcomplex reveals how WDR5 is recruited into the NSL complex via conserved linear motifs of KANSL1 and KANSL2. Using structure-based KANSL1 mutants in transgenic flies, we show that the KANSL1-WDR5 interaction is required for proper assembly, efficient recruitment of the NSL complex to target promoters, and fly viability. Our data clearly show that the interactions of WDR5 with the MOF-containing NSL complex and MLL/COMPASS histone methyltransferase complexes are mutually exclusive. We propose that rather than being a shared subunit, WDR5 plays an important role in assembling distinct histone-modifying complexes with different epigenetic regulatory roles.

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Language(s): eng - English
 Dates: 2014
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Type: Peer
 Identifiers: eDoc: 701111
 Degree: -

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Title: Genes and Development
Source Genre: Journal
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Publ. Info: Cold Spring Harbor Laboratory Press
Pages: - Volume / Issue: 28 Sequence Number: - Start / End Page: 929 - 942 Identifier: ISSN: 0890-9369
CoNE: https://pure.mpg.de/cone/journals/resource/954925557453