Structural Basis of the Chromodomain of Cbx3 Bound to Methylated Peptides from Histone H1 and G9a

Overview

Journal PLoS One

Specialties General Medicine
Science

Date 2012 Apr 20

PMID 22514736

Citations 15

Authors

Jianbin Ruan

Hui Ouyang

Maria F Amaya

Mani Ravichandran

Peter Loppnau

Jinrong Min

Jianye Zang

Affiliations

Soon will be listed here.

Abstract

Background: HP1 proteins are highly conserved heterochromatin proteins, which have been identified to be structural adapters assembling a variety of macromolecular complexes involved in regulation of gene expression, chromatin remodeling and heterochromatin formation. Much evidence shows that HP1 proteins interact with numerous proteins including methylated histones, histone methyltransferases and so on. Cbx3 is one of the paralogues of HP1 proteins, which has been reported to specifically recognize trimethylated histone H3K9 mark, and a consensus binding motif has been defined for the Cbx3 chromodomain.

Methodology/principal Findings: Here, we found that the Cbx3 chromodomain can bind to H1K26me2 and G9aK185me3 with comparable binding affinities compared to H3K9me3. We also determined the crystal structures of the human Cbx3 chromodomain in complex with dimethylated histone H1K26 and trimethylated G9aK185 peptides, respectively. The complex structures unveil that the Cbx3 chromodomain specifically bind methylated histone H1K26 and G9aK185 through a conserved mechanism.

Conclusions/significance: The Cbx3 chromodomain binds with comparable affinities to all of the methylated H3K9, H1K26 and G9aK185 peptides. It is suggested that Cbx3 may regulate gene expression via recognizing both histones and non-histone proteins.

Citing Articles

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Integrated Lactylome Characterization Reveals the Molecular Dynamics of Protein Regulation in Gastrointestinal Cancers.

Duan Y, Zhan H, Wang Q, Li B, Gao H, Liu D Adv Sci (Weinh). 2024; 11(35):e2400227.

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CBX3 Regulated By YBX1 Promotes Smoking-induced Pancreatic Cancer Progression via Inhibiting SMURF2 Expression.

Zhang H, Yu H, Ren D, Sun Y, Guo F, Cai H Int J Biol Sci. 2022; 18(8):3484-3497.

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The missing link: emerging trends for H1 variant-specific functions.

Prendergast L, Reinberg D Genes Dev. 2021; 35(1-2):40-58.

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Discovery, expression, cellular localization, and molecular properties of a novel, alternative spliced HP1γ isoform, lacking the chromoshadow domain.

Mathison A, Milech de Assuncao T, Dsouza N, Williams M, Zimmermann M, Urrutia R PLoS One. 2020; 15(2):e0217452.

PMID: 32027651 PMC: 7004349. DOI: 10.1371/journal.pone.0217452.

References

Lu A, Zougman A, Pudelko M, Bebenek M, Ziolkowski P, Mann M . Mapping of lysine monomethylation of linker histones in human breast and its cancer. J Proteome Res. 2009; 8(9):4207-15. DOI: 10.1021/pr9000652. View

Kiyomitsu T, Iwasaki O, Obuse C, Yanagida M . Inner centromere formation requires hMis14, a trident kinetochore protein that specifically recruits HP1 to human chromosomes. J Cell Biol. 2010; 188(6):791-807. PMC: 2845078. DOI: 10.1083/jcb.200908096. View

Nakayama J, Rice J, Strahl B, Allis C, Grewal S . Role of histone H3 lysine 9 methylation in epigenetic control of heterochromatin assembly. Science. 2001; 292(5514):110-3. DOI: 10.1126/science.1060118. View

Fanti L, Pimpinelli S . HP1: a functionally multifaceted protein. Curr Opin Genet Dev. 2008; 18(2):169-74. DOI: 10.1016/j.gde.2008.01.009. View

Xu C, Bian C, Lam R, Dong A, Min J . The structural basis for selective binding of non-methylated CpG islands by the CFP1 CXXC domain. Nat Commun. 2011; 2:227. PMC: 3072069. DOI: 10.1038/ncomms1237. View

Kwon S, Workman J . The changing faces of HP1: From heterochromatin formation and gene silencing to euchromatic gene expression: HP1 acts as a positive regulator of transcription. Bioessays. 2011; 33(4):280-9. DOI: 10.1002/bies.201000138. View

Fujita N, Watanabe S, Ichimura T, Tsuruzoe S, Shinkai Y, Tachibana M . Methyl-CpG binding domain 1 (MBD1) interacts with the Suv39h1-HP1 heterochromatic complex for DNA methylation-based transcriptional repression. J Biol Chem. 2003; 278(26):24132-8. DOI: 10.1074/jbc.M302283200. View

Daujat S, Zeissler U, Waldmann T, Happel N, Schneider R . HP1 binds specifically to Lys26-methylated histone H1.4, whereas simultaneous Ser27 phosphorylation blocks HP1 binding. J Biol Chem. 2005; 280(45):38090-5. DOI: 10.1074/jbc.C500229200. View

Huang Y, Myers M, Xu R . Crystal structure of the HP1-EMSY complex reveals an unusual mode of HP1 binding. Structure. 2006; 14(4):703-12. DOI: 10.1016/j.str.2006.01.007. View

10.

Davis I, Murray L, Richardson J, Richardson D . MOLPROBITY: structure validation and all-atom contact analysis for nucleic acids and their complexes. Nucleic Acids Res. 2004; 32(Web Server issue):W615-9. PMC: 441536. DOI: 10.1093/nar/gkh398. View

11.

Eissenberg J, Elgin S . The HP1 protein family: getting a grip on chromatin. Curr Opin Genet Dev. 2000; 10(2):204-10. DOI: 10.1016/s0959-437x(00)00058-7. View

12.

Kim H, Heo K, Choi J, Kim K, An W . Histone variant H3.3 stimulates HSP70 transcription through cooperation with HP1γ. Nucleic Acids Res. 2011; 39(19):8329-41. PMC: 3201866. DOI: 10.1093/nar/gkr529. View

13.

Happel N, Doenecke D . Histone H1 and its isoforms: contribution to chromatin structure and function. Gene. 2008; 431(1-2):1-12. DOI: 10.1016/j.gene.2008.11.003. View

14.

Honda S, Selker E . Direct interaction between DNA methyltransferase DIM-2 and HP1 is required for DNA methylation in Neurospora crassa. Mol Cell Biol. 2008; 28(19):6044-55. PMC: 2547014. DOI: 10.1128/MCB.00823-08. View

15.

Min J, Allali-Hassani A, Nady N, Qi C, Ouyang H, Liu Y . L3MBTL1 recognition of mono- and dimethylated histones. Nat Struct Mol Biol. 2007; 14(12):1229-30. DOI: 10.1038/nsmb1340. View

16.

Xu C, Bian C, Yang W, Galka M, Ouyang H, Chen C . Binding of different histone marks differentially regulates the activity and specificity of polycomb repressive complex 2 (PRC2). Proc Natl Acad Sci U S A. 2010; 107(45):19266-71. PMC: 2984210. DOI: 10.1073/pnas.1008937107. View

17.

Otwinowski Z, Minor W . Processing of X-ray diffraction data collected in oscillation mode. Methods Enzymol. 1997; 276:307-26. DOI: 10.1016/S0076-6879(97)76066-X. View

18.

JONES D, Cowell I, Singh P . Mammalian chromodomain proteins: their role in genome organisation and expression. Bioessays. 2000; 22(2):124-37. DOI: 10.1002/(SICI)1521-1878(200002)22:2<124::AID-BIES4>3.0.CO;2-E. View

19.

Shareef M, King C, Damaj M, Badagu R, Huang D, KELLUM R . Drosophila heterochromatin protein 1 (HP1)/origin recognition complex (ORC) protein is associated with HP1 and ORC and functions in heterochromatin-induced silencing. Mol Biol Cell. 2001; 12(6):1671-85. PMC: 37332. DOI: 10.1091/mbc.12.6.1671. View

20.

Yamamoto K, Sonoda M . Self-interaction of heterochromatin protein 1 is required for direct binding to histone methyltransferase, SUV39H1. Biochem Biophys Res Commun. 2003; 301(2):287-92. DOI: 10.1016/s0006-291x(02)03021-8. View