UHRF1 PHD domain (human recombinant)

Recognition of epigenetic marks can be mediated by small modular protein units of ~50 amino acids called Plant Homeodomain (PHD) fingers. PHD fingers are zinc binding domains that have a Cys4-His-Cys3 motif and are found in more than 100 nuclear proteins that play a role in regulating chromatin.¹ PHD domains often work with other protein regions, such as bromodomains and Tudor domains, to recognize post-translational modifications in many proteins.¹ Ubiquitin-like with PHD and ring finger domains 1 (UHRF1) is a multidomain-containing nuclear protein known to bind chromatin and participate in the maintenance of DNA methylation.^2,3 The SET and RING associated domain of UHRF1, also called the YDG motif, binds methyl cytosines, while trimethylated histone H3 lysine 9 (H3K9me3) and unmethylated histone H3 Arginine 2 (H3R2me0) are recognized by the tandem Tudor-like domains and the PHD domain, respectively.^4,5,6,7,8,9 Some evidence suggests the tandem Tudor-like region and adjacent PHD domain may operate together to recognize H3K9me3.¹⁰ The combinatorial recognition of the histone tail region and hemi-methylated DNA functions to regulate gene silencing by directly interacting with DNA (cytosine-5)-methyltransferase 1.^11,2,12 UHRF1 also posseses E3 ubiquitin ligase activity toward histone H3 and the tumor suppressor promyelocytic leukemia protein.^7,13 This protein product contains the PHD finger region of UHRF1.

WARNING This product is not for human or veterinary use.

1. Bienz, M. The PHD finger, a nuclear protein-interaction domain. Trends Biochem. Sci. 31(1), 35-40 (2006).

2. Bostick, M., Kim, J.K., Estève, P.O., et al. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 317(5845), 1760-1764 (2007).

3. Hopfner, R., Mousli, M., Jeltsch, J.M., et al. ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase II α expression. Cancer Res. 60(1), 121-128 (2000).

4. Unoki, M., Nishidate, T., and Nakamura, Y. ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain. Oncogene 23(46), 7601-7610 (2004).

5. Sharif, J., Muto, M., Takebayashi, S.i., et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 450(7171), 908-912 (2007).

6. Avvakumov, G.V., Walker, J.R., Xue, S., et al. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1. Nature 455(7214), 822-825 (2008).

7. Karagianni, P., Amazit, L., Qin, J., et al. ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation. Mol. Cell. Biol. 28(2), 705-717 (2008).

8. Hu, L., Li, Z., Wang, P., et al. Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2. Cell Res. 21(9), 1374-1378 (2011).

9. Lallous, N., Legrand, P., McEwen, A.G., et al. The PHD finger of human UHRF1 reveals a new subgroup of unmethylated histone H3 tail readers. PLoS One 6(11), e27599 (2011).

10. Xie, S., Jakoncic, J., and Qian, C. UHRF1 double tudor domain and the adjacent PHD finger act together to recognize K9me3-containing histone H3 tail. J. Mol. Biol. 415(2), 318-328 (2012).

11. Felle, M., Joppien, S., Németh, A., et al. The USP7/Dnmt1 complex stimulates the DNA methylation activity of Dnmt1 and regulates the stability of UHRF1. Nucleic Acids Res. 39(19), 8355-8365 (2011).

12. Rothbart, S.B., Krajewski, K., Nady, N., et al. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat. Struct. Mol. Biol. 19(11), 1155-1160 (2012).

13. Guan, D., Factor, D., Liu, Y., et al. The epigenetic regulator UHRF1 promotes ubiquitination-mediated degradation of the tumor-suppressor protein promyelocytic leukemia protein. Oncogene 32(33), 3819-3828 (2013).