Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Nov 27;187(24):6849-6864.e18.
doi: 10.1016/j.cell.2024.09.007. Epub 2024 Oct 1.

Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler

Robert K Louder  1 , Giho Park  2 , Ziyang Ye  3 , Justin S Cha  4 , Anne M Gardner  4 , Qin Lei  3 , Anand Ranjan  3 , Eva Höllmüller  5 , Florian Stengel  6 , B Franklin Pugh  4 , Carl Wu  7
Affiliations

Molecular basis of global promoter sensing and nucleosome capture by the SWR1 chromatin remodeler

Robert K Louder et al. Cell. .

Abstract

The SWR1 chromatin remodeling complex is recruited to +1 nucleosomes downstream of transcription start sites of eukaryotic promoters, where it exchanges histone H2A for the specialized variant H2A.Z. Here, we use cryoelectron microscopy (cryo-EM) to resolve the structural basis of the SWR1 interaction with free DNA, revealing a distinct open conformation of the Swr1 ATPase that enables sliding from accessible DNA to nucleosomes. A complete structural model of the SWR1-nucleosome complex illustrates critical roles for Swc2 and Swc3 subunits in oriented nucleosome engagement by SWR1. Moreover, an extended DNA-binding α helix within the Swc3 subunit enables sensing of nucleosome linker length and is essential for SWR1-promoter-specific recruitment and activity. The previously unresolved N-SWR1 subcomplex forms a flexible extended structure, enabling multivalent recognition of acetylated histone tails by reader domains to further direct SWR1 toward the +1 nucleosome. Altogether, our findings provide a generalizable mechanism for promoter-specific targeting of chromatin and transcription complexes.

Keywords: +1 nucleosome; DNA sliding; H2A.Z; SWR1; chromatin remodeler; cryo-EM; histone acetylation; histone exchange; histone reader; promoter.

PubMed Disclaimer

Conflict of interest statement

Declaration of interests B.F.P. is an owner of and has a financial interest in Peconic, which uses the ChIP-exo technology (US Patent 20100323361A1) implemented in this study and could potentially benefit from the outcomes of this research.

References

    1. Arents G, Burlingame RW, Wang BC, Love WE, and Moudrianakis EN (1991). The nucleosomal core histone octamer at 3.1 A resolution: a tripartite protein assembly and a left-handed superhelix. Proc. Natl. Acad. Sci. U. S. A 88, 10148–10152. 10.1073/pnas.88.22.10148. - DOI - PMC - PubMed
    1. Luger K, Mäder AW, Richmond RK, Sargent DF, and Richmond TJ (1997). Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 389, 251–260. 10.1038/38444. - DOI - PubMed
    1. Kornberg RD, and Lorch Y (1999). Twenty-five years of the nucleosome, fundamental particle of the eukaryote chromosome. Cell 98, 285–294. 10.1016/s0092-8674(00)81958-3. - DOI - PubMed
    1. Giaimo BD, Ferrante F, Herchenröther A, Hake SB, and Borggrefe T (2019). The histone variant H2A.Z in gene regulation. Epigenetics Chromatin 12, 37. 10.1186/s13072-019-0274-9. - DOI - PMC - PubMed
    1. Raisner RM, Hartley PD, Meneghini MD, Bao MZ, Liu CL, Schreiber SL, Rando OJ, and Madhani HD (2005). Histone variant H2A.Z marks the 5’ ends of both active and inactive genes in euchromatin. Cell 123, 233–248. 10.1016/j.cell.2005.10.002. - DOI - PMC - PubMed

MeSH terms

LinkOut - more resources