CBX3 (human recombinant)

The heterochromatin protein 1 (HP1) family, which consists of isoforms HP1-α (CBX5), HP1-β (CBX1), and HP1-γ (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 that connects the two.² Extensive post-translational modifications have been observed and mapped on the CBX proteins.³ The chromodomain of CBX3 has been shown to recognize methylated histone H3 lysine 9, methylated histone H1 lysine 26, and G9A methylated at lysine 185.⁴ CBX3 associates with the exons of a subset of actively transcribed genes, and loss of CBX3 results in accumulation of unspliced mRNA from that subset of genes.^5,6 Further, CBX3 suppresses Nanog gene transcription in pre-induced pluripotent stem cells and long terminal repeat protein expression in HIV-1 infected cells.^6,7 Knockdown of CBX3 by siRNA in cells latently infected with HIV-1 leads to virus reactivation.⁸ CBX3 has been proposed to be a biomarker for tumor stem cells in osteosarcoma.⁹

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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. Ruan, J., Ouyang, H., Amaya, M.F., et al. Structural basis of the chromodomain of Cbx3 bound to methylated peptides from histone H1 and G9a. PLoS One 7(4), e35376 (2012).

5. Smallwood, A., Hon, G.C., Jin, F., et al. CBX3 regulates efficient RNA processing genome-wide. Genome Res. 22(8), 1426-1436 (2012).

6. Sridharan, R., Gonzales-Cope, M., Chronis, C., et al. Proteomic and genomic approaches reveal critical functions of H3K9 methylation and heterochromatin protein-1γ in reprogramming to pluripotency. Nat. Cell Biol. 15(7), 872-882 (2013).

7. Mateescu, B., Bourachot, B., Rachez, C., et al. Regulation of an inducible promoter by an HP1β-HP1γ switch. EMBO J. 9(3), 267-272 (2008).

8. du Chéné, I., Basyuk, E., Lin, Y.L., et al. Suv39H1 and HP1γ are responsible for chromatin-mediated HIV-1 transcriptional silencing and post-integration latency. EMBO J. 26(2), 424-435 (2007).

9. Saini, V., Hose, C.D., Monks, A., et al. Identification of CBX3 and ABCA5 as putative biomarkers for tumor stem cells in osteosarcoma. PLoS One 7(8), e41401 (2014).