Structural highlights
Function
[H2B11_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. [ISW1_YEAST] Catalytic component of ISW1-type complexes, which act by remodeling the chromatin by catalyzing an ATP-dependent alteration in the structure of nucleosomal DNA. They are involved in coordinating transcriptional repression, activation and elongation phases. The ISW1A complex represses gene expression at initiation through specific positioning of a promoter proximal dinucleosome. The ISW1B complex acts within coding regions to control the amount of RNA polymerase II released into productive elongation and to coordinate elongation with termination and pre-mRNA processing.[1] [2] [3] [4] [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.
Publication Abstract from PubMed
Chromatin remodelers are diverse enzymes, and different models have been proposed to explain how these proteins work. Here we report the 3.3 A-resolution cryogenic electron microscopy (cryo-EM) structures of Saccharomyces cerevisiae ISWI (ISW1) in complex with the nucleosome in adenosine diphosphate (ADP)-bound and ADP-BeFx-bound states. The data show that after nucleosome binding, ISW1 is activated by substantial rearrangement of the catalytic domains, with the regulatory AutoN domain packing the first RecA-like core and the NegC domain being disordered. The high-resolution structure reveals local DNA distortion and translocation induced by ISW1 in the ADP-bound state, which is essentially identical to that induced by the Snf2 chromatin remodeler, suggesting a common mechanism of DNA translocation. The histone core remains largely unperturbed, and prevention of histone distortion by crosslinking did not inhibit the activity of yeast ISW1 or its human homolog. Together, our findings suggest a general mechanism of chromatin remodeling involving local DNA distortion without notable histone deformation.
Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling.,Yan L, Wu H, Li X, Gao N, Chen Z Nat Struct Mol Biol. 2019 Mar 13. pii: 10.1038/s41594-019-0199-9. doi:, 10.1038/s41594-019-0199-9. PMID:30872815[5]
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine.
References
- ↑ Tsukiyama T, Palmer J, Landel CC, Shiloach J, Wu C. Characterization of the imitation switch subfamily of ATP-dependent chromatin-remodeling factors in Saccharomyces cerevisiae. Genes Dev. 1999 Mar 15;13(6):686-97. PMID:10090725
- ↑ Kent NA, Karabetsou N, Politis PK, Mellor J. In vivo chromatin remodeling by yeast ISWI homologs Isw1p and Isw2p. Genes Dev. 2001 Mar 1;15(5):619-26. PMID:11238381 doi:http://dx.doi.org/10.1101/gad.190301
- ↑ Morillon A, Karabetsou N, O'Sullivan J, Kent N, Proudfoot N, Mellor J. Isw1 chromatin remodeling ATPase coordinates transcription elongation and termination by RNA polymerase II. Cell. 2003 Nov 14;115(4):425-35. PMID:14622597
- ↑ Vary JC Jr, Gangaraju VK, Qin J, Landel CC, Kooperberg C, Bartholomew B, Tsukiyama T. Yeast Isw1p forms two separable complexes in vivo. Mol Cell Biol. 2003 Jan;23(1):80-91. PMID:12482963
- ↑ Yan L, Wu H, Li X, Gao N, Chen Z. Structures of the ISWI-nucleosome complex reveal a conserved mechanism of chromatin remodeling. Nat Struct Mol Biol. 2019 Mar 13. pii: 10.1038/s41594-019-0199-9. doi:, 10.1038/s41594-019-0199-9. PMID:30872815 doi:http://dx.doi.org/10.1038/s41594-019-0199-9
