Vimentin Binds to G-quadruplex Repeats Found at Telomeres and Gene Promoters

Overview

Journal Nucleic Acids Res

Publisher Oxford University Press

Specialty Biochemistry

Date 2022 Jan 31

PMID 35100428

Authors

Silvia Ceschi

Michele Berselli

Marta Cozzaglio

Mery Giantin

Stefano Toppo

Barbara Spolaore

Claudia Sissi

Affiliations

Soon will be listed here.

Abstract

G-quadruplex (G4) structures that can form at guanine-rich genomic sites, including telomeres and gene promoters, are actively involved in genome maintenance, replication, and transcription, through finely tuned interactions with protein networks. In the present study, we identified the intermediate filament protein Vimentin as a binder with nanomolar affinity for those G-rich sequences that give rise to at least two adjacent G4 units, named G4 repeats. This interaction is supported by the N-terminal domains of soluble Vimentin tetramers. The selectivity of Vimentin for G4 repeats versus individual G4s provides an unprecedented result. Based on GO enrichment analysis performed on genes having putative G4 repeats within their core promoters, we suggest that Vimentin recruitment at these sites may contribute to the regulation of gene expression during cell development and migration, possibly by reshaping the local higher-order genome topology, as already reported for lamin B.

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References

Pascual-Reguant L, Blanco E, Galan S, Le Dily F, Cuartero Y, Serra-Bardenys G . Lamin B1 mapping reveals the existence of dynamic and functional euchromatin lamin B1 domains. Nat Commun. 2018; 9(1):3420. PMC: 6109041. DOI: 10.1038/s41467-018-05912-z. View

Gimenez y Ribotta M, Maurice T, Babinet C, Privat A . Cerebellar defect and impaired motor coordination in mice lacking vimentin. Glia. 1999; 25(1):33-43. View

Buchwalter A, Kaneshiro J, Hetzer M . Coaching from the sidelines: the nuclear periphery in genome regulation. Nat Rev Genet. 2018; 20(1):39-50. PMC: 6355253. DOI: 10.1038/s41576-018-0063-5. View

Sen D, Gilbert W . Formation of parallel four-stranded complexes by guanine-rich motifs in DNA and its implications for meiosis. Nature. 1988; 334(6180):364-6. DOI: 10.1038/334364a0. View

Soellner P, Quinlan R, Franke W . Identification of a distinct soluble subunit of an intermediate filament protein: tetrameric vimentin from living cells. Proc Natl Acad Sci U S A. 1985; 82(23):7929-33. PMC: 390883. DOI: 10.1073/pnas.82.23.7929. View

Snider N, Omary M . Assays for Posttranslational Modifications of Intermediate Filament Proteins. Methods Enzymol. 2016; 568:113-38. PMC: 4855289. DOI: 10.1016/bs.mie.2015.09.005. View

Symmons O, Pan L, Remeseiro S, Aktas T, Klein F, Huber W . The Shh Topological Domain Facilitates the Action of Remote Enhancers by Reducing the Effects of Genomic Distances. Dev Cell. 2016; 39(5):529-543. PMC: 5142843. DOI: 10.1016/j.devcel.2016.10.015. View

Murray M, Mendez M, Janmey P . Substrate stiffness regulates solubility of cellular vimentin. Mol Biol Cell. 2013; 25(1):87-94. PMC: 3873896. DOI: 10.1091/mbc.E13-06-0326. View

Petraccone L, Spink C, Trent J, Garbett N, Mekmaysy C, Giancola C . Structure and stability of higher-order human telomeric quadruplexes. J Am Chem Soc. 2011; 133(51):20951-61. PMC: 3244555. DOI: 10.1021/ja209192a. View

10.

Lieberman-Aiden E, van Berkum N, Williams L, Imakaev M, Ragoczy T, Telling A . Comprehensive mapping of long-range interactions reveals folding principles of the human genome. Science. 2009; 326(5950):289-93. PMC: 2858594. DOI: 10.1126/science.1181369. View

11.

Mucke N, Kammerer L, Winheim S, Kirmse R, Krieger J, Mildenberger M . Assembly Kinetics of Vimentin Tetramers to Unit-Length Filaments: A Stopped-Flow Study. Biophys J. 2018; 114(10):2408-2418. PMC: 6129470. DOI: 10.1016/j.bpj.2018.04.032. View

12.

Tolstonog G, MOTHES E, Shoeman R, Traub P . Isolation of SDS-stable complexes of the intermediate filament protein vimentin with repetitive, mobile, nuclear matrix attachment region, and mitochondrial DNA sequence elements from cultured mouse and human fibroblasts. DNA Cell Biol. 2001; 20(9):531-54. DOI: 10.1089/104454901317094954. View

13.

Laemmli U . Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature. 1970; 227(5259):680-5. DOI: 10.1038/227680a0. View

14.

Amato J, Madanayake T, Iaccarino N, Novellino E, Randazzo A, Hurley L . HMGB1 binds to the KRAS promoter G-quadruplex: a new player in oncogene transcriptional regulation?. Chem Commun (Camb). 2018; 54(68):9442-9445. PMC: 6234227. DOI: 10.1039/c8cc03614d. View

15.

Gesson K, Rescheneder P, Skoruppa M, von Haeseler A, Dechat T, Foisner R . A-type lamins bind both hetero- and euchromatin, the latter being regulated by lamina-associated polypeptide 2 alpha. Genome Res. 2016; 26(4):462-73. PMC: 4817770. DOI: 10.1101/gr.196220.115. View

16.

Law M, Lower K, Voon H, Hughes J, Garrick D, Viprakasit V . ATR-X syndrome protein targets tandem repeats and influences allele-specific expression in a size-dependent manner. Cell. 2010; 143(3):367-78. DOI: 10.1016/j.cell.2010.09.023. View

17.

Huang D, Sherman B, Lempicki R . Systematic and integrative analysis of large gene lists using DAVID bioinformatics resources. Nat Protoc. 2009; 4(1):44-57. DOI: 10.1038/nprot.2008.211. View

18.

Zhao C, Li Q . Altered profiles of nuclear matrix proteins during the differentiation of human gastric mucous adenocarcinoma MGc80-3 cells. World J Gastroenterol. 2005; 11(30):4628-33. PMC: 4615401. DOI: 10.3748/wjg.v11.i30.4628. View

19.

Strouhalova K, Prechova M, Gandalovicova A, Brabek J, Gregor M, Rosel D . Vimentin Intermediate Filaments as Potential Target for Cancer Treatment. Cancers (Basel). 2020; 12(1). PMC: 7017239. DOI: 10.3390/cancers12010184. View

20.

Li L, Williams P, Ren W, Wang M, Gao Z, Miao W . YY1 interacts with guanine quadruplexes to regulate DNA looping and gene expression. Nat Chem Biol. 2020; 17(2):161-168. PMC: 7854983. DOI: 10.1038/s41589-020-00695-1. View