| Structural highlights
Disease
[SMCA5_HUMAN] Extraskeletal Ewing sarcoma.
Function
[H2A1_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [H4_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling. [SMCA5_HUMAN] Helicase that possesses intrinsic ATP-dependent nucleosome-remodeling activity. Complexes containing SMARCA5 are capable of forming ordered nucleosome arrays on chromatin; this may require intact histone H4 tails. Also required for replication of pericentric heterochromatin in S-phase specifically in conjunction with BAZ1A. Probably plays a role in repression of polI dependent transcription of the rDNA locus, through the recruitment of the SIN3/HDAC1 corepressor complex to the rDNA promoter. Essential component of the WICH complex, a chromatin remodeling complex that mobilizes nucleosomes and reconfigures irregular chromatin to a regular nucleosomal array structure. The WICH complex regulates the transcription of various genes, has a role in RNA polymerase I and RNA polymerase III transcription, mediates the histone H2AX phosphorylation at 'Tyr-142', and is involved in the maintenance of chromatin structures during DNA replication processes. Essential component of the NoRC (nucleolar remodeling complex) complex, a complex that mediates silencing of a fraction of rDNA by recruiting histone-modifying enzymes and DNA methyltransferases, leading to heterochromatin formation and transcriptional silencing.[1] [2] [3] [4] [5] [6] [7] [H32_XENLA] Core component of nucleosome. Nucleosomes wrap and compact DNA into chromatin, limiting DNA accessibility to the cellular machineries which require DNA as a template. Histones thereby play a central role in transcription regulation, DNA repair, DNA replication and chromosomal stability. DNA accessibility is regulated via a complex set of post-translational modifications of histones, also called histone code, and nucleosome remodeling.
Publication Abstract from PubMed
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.
Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome.,Armache JP, Gamarra N, Johnson SL, Leonard JD, Wu S, Narlikar GJ, Cheng Y Elife. 2019 Jun 18;8. pii: 46057. doi: 10.7554/eLife.46057. PMID:31210637[8]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
See Also
References
- ↑ Poot RA, Dellaire G, Hulsmann BB, Grimaldi MA, Corona DF, Becker PB, Bickmore WA, Varga-Weisz PD. HuCHRAC, a human ISWI chromatin remodelling complex contains hACF1 and two novel histone-fold proteins. EMBO J. 2000 Jul 3;19(13):3377-87. PMID:10880450 doi:http://dx.doi.org/10.1093/emboj/19.13.3377
- ↑ Bozhenok L, Wade PA, Varga-Weisz P. WSTF-ISWI chromatin remodeling complex targets heterochromatic replication foci. EMBO J. 2002 May 1;21(9):2231-41. PMID:11980720 doi:10.1093/emboj/21.9.2231
- ↑ Hakimi MA, Bochar DA, Schmiesing JA, Dong Y, Barak OG, Speicher DW, Yokomori K, Shiekhattar R. A chromatin remodelling complex that loads cohesin onto human chromosomes. Nature. 2002 Aug 29;418(6901):994-8. doi: 10.1038/nature01024. PMID:12198550 doi:http://dx.doi.org/10.1038/nature01024
- ↑ Collins N, Poot RA, Kukimoto I, Garcia-Jimenez C, Dellaire G, Varga-Weisz PD. An ACF1-ISWI chromatin-remodeling complex is required for DNA replication through heterochromatin. Nat Genet. 2002 Dec;32(4):627-32. doi: 10.1038/ng1046. Epub 2002 Nov 18. PMID:12434153 doi:http://dx.doi.org/10.1038/ng1046
- ↑ Loyola A, Huang JY, LeRoy G, Hu S, Wang YH, Donnelly RJ, Lane WS, Lee SC, Reinberg D. Functional analysis of the subunits of the chromatin assembly factor RSF. Mol Cell Biol. 2003 Oct;23(19):6759-68. PMID:12972596
- ↑ Poot RA, Bozhenok L, van den Berg DL, Steffensen S, Ferreira F, Grimaldi M, Gilbert N, Ferreira J, Varga-Weisz PD. The Williams syndrome transcription factor interacts with PCNA to target chromatin remodelling by ISWI to replication foci. Nat Cell Biol. 2004 Dec;6(12):1236-44. Epub 2004 Nov 14. PMID:15543136 doi:10.1038/ncb1196
- ↑ Cavellan E, Asp P, Percipalle P, Farrants AK. The WSTF-SNF2h chromatin remodeling complex interacts with several nuclear proteins in transcription. J Biol Chem. 2006 Jun 16;281(24):16264-71. Epub 2006 Apr 9. PMID:16603771 doi:10.1074/jbc.M600233200
- ↑ Armache JP, Gamarra N, Johnson SL, Leonard JD, Wu S, Narlikar GJ, Cheng Y. Cryo-EM structures of remodeler-nucleosome intermediates suggest allosteric control through the nucleosome. Elife. 2019 Jun 18;8. pii: 46057. doi: 10.7554/eLife.46057. PMID:31210637 doi:http://dx.doi.org/10.7554/eLife.46057
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