CBX5 (human recombinant)

The heterochromatin protein 1 (HP1) family, which consists of three isoforms HP1α (CBX5), HP1β (CBX1) and HP1γ (CBX3) are chromatin-associated proteins involved in gene regulation and heterochromatin formation.¹ CBX proteins have an N-terminal chromodomain, a C-terminal chromoshadow domain, and a hinge domain which connects the two.² Extensive post-translational modifications have been observed and mapped on the CBX proteins.³ The chromodomain of CBX5 has been shown to recognize di- and tri-methylated lysine 9 on histone H3 (H3K9me2 and H3K9me3), with a preference for H3K9me3. Binding of CBX5 to methylated histones leads to gene silencing and heterochromatin formation.^1,4 H3K9 trimethylation by the methyltransferase SETDB1 creates a binding site for recruitment of CBX5, leading to chromatin condensation and gene silencing.⁵ The chromoshadow domain facilitates protein-protein interactions like homodimerization and recruitment of nuclear proteins involved in transcriptional regulation.⁶ The chromoshadow domain is also responsible for recruitment to sites of DNA damage, where CBX5 helps to reorganize chromatin as part of the DNA damage response system.⁷

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1. Lachner, M., O'Carroll, D., Rea, S., et al. Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins. Nature 410(6824), 116-120 (2001).

2. Kwon, S.H., and Workman, J.L. The changing faces of HP1: From heterochromatin formation and gene silencing to euchromatic gene expression. BioEssays 33(4), 280-289 (2011).

3. LeRoy, G., Weston, J.T., Zee, B.M., et al. Heterochromatin protein 1 is extensively decorated with histone code-like post-translational modifications. Mol. Cell. Proteomics 8(11), 2432-2442 (2009).

4. Kaustov, L., Ouyang, H., Amaya, M., et al. Recognition and specificity determinants of the human Cbx chromodomains. The Journal of Biological Chemisty 286(1), 521-529 (2011).

5. Verschure, P.J., van der Kraan, I., de Leeuw, W., et al. In vivo HP1 targeting causes large-scale chromatin condensation and enhanced histone lysine methylation. Mol. Cell. Biol. 25(11), 4552-4564 (2005).

6. Richart, A.N., Brunner, C.I.W., Stott, K., et al. Characterization of the chromoshadow domain-mediated binding of heterochromatin protein 1α (HP1α) to histone H3. The Journal of Biological Chemisty 287(22), 18730-18737 (2012).

7. Luijsterburg, M.S., Dinant, C., Lans, H., et al. Heterochromatin protein 1 is recruited to various types of DNA damage. The Journal of Biological Chemisty 185(4), 577-586 (2009).