6ne3 Citations

Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome.

Abstract

The SNF2h remodeler slides nucleosomes most efficiently as a dimer, yet how the two protomers avoid a tug-of-war is unclear. Furthermore, SNF2h couples histone octamer deformation to nucleosome sliding, but the underlying structural basis remains unknown. Here we present cryo-EM structures of SNF2h-nucleosome complexes with ADP-BeFx that capture two potential reaction intermediates. In one structure, histone residues near the dyad and in the H2A-H2B acidic patch, distal to the active SNF2h protomer, appear disordered. The disordered acidic patch is expected to inhibit the second SNF2h protomer, while disorder near the dyad is expected to promote DNA translocation. The other structure doesn't show octamer deformation, but surprisingly shows a 2 bp translocation. FRET studies indicate that ADP-BeFx predisposes SNF2h-nucleosome complexes for an elemental translocation step. We propose a model for allosteric control through the nucleosome, where one SNF2h protomer promotes asymmetric octamer deformation to inhibit the second protomer, while stimulating directional DNA translocation.

Reviews - 6ne3 mentioned but not cited (3)

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Articles - 6ne3 mentioned but not cited (4)

  1. Pathogenic variants in SMARCA5, a chromatin remodeler, cause a range of syndromic neurodevelopmental features. Li D, Wang Q, Gong NN, Kurolap A, Feldman HB, Boy N, Brugger M, Grand K, McWalter K, Guillen Sacoto MJ, Wakeling E, Hurst J, March ME, Bhoj EJ, Nowaczyk MJM, Gonzaga-Jauregui C, Mathew M, Dava-Wala A, Siemon A, Bartholomew D, Huang Y, Lee H, Martinez-Agosto JA, Schwaibold EMC, Brunet T, Choukair D, Pais LS, White SM, Christodoulou J, Brown D, Lindstrom K, Grebe T, Tiosano D, Kayser MS, Tan TY, Deardorff MA, Song Y, Hakonarson H. Sci Adv 7 eabf2066 (2021)
  2. Chromatin remodeling of histone H3 variants by DDM1 underlies epigenetic inheritance of DNA methylation. Lee SC, Adams DW, Ipsaro JJ, Cahn J, Lynn J, Kim HS, Berube B, Major V, Calarco JP, LeBlanc C, Bhattacharjee S, Ramu U, Grimanelli D, Jacob Y, Voigt P, Joshua-Tor L, Martienssen RA. Cell 186 4100-4116.e15 (2023)
  3. Long non-coding RNA lncMGC mediates the expression of TGF-β-induced genes in renal cells via nucleosome remodelers. Kato M, Chen Z, Das S, Wu X, Wang J, Li A, Chen W, Tsark W, Tunduguru R, Lanting L, Wang M, Moore R, Kalkum M, Abdollahi M, Natarajan R. Front Mol Biosci 10 1204124 (2023)
  4. research-article Functionalized graphene-oxide grids enable high-resolution cryo-EM structures of the SNF2h-nucleosome complex without crosslinking. Chio US, Palovcak E, Autzen AAA, Autzen HE, Muñoz EN, Yu Z, Wang F, Agard DA, Armache JP, Narlikar GJ, Cheng Y. bioRxiv 2023.06.20.545796 (2023)


Reviews citing this publication (11)

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Articles citing this publication (22)

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  5. Structure and dynamics of the chromatin remodeler ALC1 bound to a PARylated nucleosome. Bacic L, Gaullier G, Sabantsev A, Lehmann LC, Brackmann K, Dimakou D, Halic M, Hewitt G, Boulton SJ, Deindl S. Elife 10 e71420 (2021)
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  7. Partial Replacement of Nucleosomal DNA with Human FACT Induces Dynamic Exposure and Acetylation of Histone H3 N-Terminal Tails. Tsunaka Y, Ohtomo H, Morikawa K, Nishimura Y. iScience 23 101641 (2020)
  8. Autoinhibitory elements of the Chd1 remodeler block initiation of twist defects by destabilizing the ATPase motor on the nucleosome. Nodelman IM, Shen Z, Levendosky RF, Bowman GD. Proc Natl Acad Sci U S A 118 e2014498118 (2021)
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  18. Letter Histone dynamics play a critical role in SNF2h-mediated nucleosome sliding. Gamarra N, Narlikar GJ. Nat Struct Mol Biol 28 548-551 (2021)
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  20. The role of auxiliary domains in modulating CHD4 activity suggests mechanistic commonality between enzyme families. Zhong Y, Moghaddas Sani H, Paudel BP, Low JKK, Silva APG, Mueller S, Deshpande C, Panjikar S, Reid XJ, Bedward MJ, van Oijen AM, Mackay JP. Nat Commun 13 7524 (2022)
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