Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns
<p>Schematic representation of ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1)’s domains with open and closed conformations. (<b>a</b>) Closed conformation of UHRF1. In the absence of methylated DNA (open lollipops), UHRF1 adopts a closed conformation with the spacer (S) facing the tandem Tudor domain (TTD) and the RING domain facing the ubiquitin-like domain (UBL). This interaction may represent a kind of auto-inhibitory mechanism as UBL exhibits analogy with ubiquitin. The SET- and RING-associated (SRA) domain faces the PHD domain. The linker (L) is the sequence between the TTD and PHD. (<b>b</b>) Open conformation of UHRF1. In the presence of hemi-methylated DNA (full lollipops on one strand) and in the presence of di/trimethylated lysine 9 on histone H3 (ocher rectangle on nucleosome) and of unmodified arginine 2 on histone H3 (blue hexagon on nucleosome), UHRF1 adopts an open conformation allowing each domain to fulfill its respective role. For instance, the RING domain can ubiquitinate histone H3 and the TTD with methylated histone H3.</p> "> Figure 2
<p>Dialogue model between UHRF1 and DNA methyltransferase 1 (DNMT1) in the presence of hemi-methylated DNA. (<b>a</b>) Model A: targeting of DNMT1 to chromatin via histone H3-dependent ubiquitination. Two molecules of ubiquitin (Ub) on the nucleosome, mediated by the RING domain of UHRF1 (dotted line), serve as an anchorage for DNMT1 via the replication focus targeting sequence (RFTS) domain. This interaction allows the alleviation of the auto-inhibitory activity of RFTS on the catalytic domain (CD) of DNMT1. Concomitantly, the TTD binds di/trimethylated lysine 9 on histone H3 (ocher rectangle on nucleosome) and the PDH binds unmodified arginine 2 on histone H3 (blue hexagon on nucleosome). (<b>b</b>) Model B: targeting of DNMT1 to chromatin via UHRF1 domain interactions. The UBL (dotted line) and SRA domain interact with the RFTS domain of UHRF1, allowing the release of the catalytic domain (CD) of DNMT1. As with model A, the TTD binds di/trimethylated lysine 9 on histone H3 (ocher rectangle on nucleosome) and the PDH binds unmodified arginine 2 on histone H3 (blue hexagon on nucleosome).</p> ">
Abstract
:1. Introduction
1.1. DNA Methylation Patterns: Layers of Epigenomes
1.2. The Role of UHRF1/DNMT1 Tandem
1.3. UHRF1 and DNMT1, Interdependent Multi-Domain Proteins
2. The UHRF1/DNMT1 Dialogue on Chromatin
2.1. The Ubiquitination of Histone H3 by UHRF1 as a Chromatin Anchorage for DNMT1: Model A
2.2. Domain–Domain Interactions between DNMT1 and UHRF1: Model B
2.3. A Conciliated Model of How the UHRF1/DNMT1 Tandem Works
3. Concluding Remarks
Author Contributions
Funding
Conflicts of Interest
References
- Bird, A. DNA methylation patterns and epigenetic memory. Genes Dev. 2002, 16, 6–21. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Schubeler, D. Function and information content of DNA methylation. Nature 2015, 517, 321–326. [Google Scholar] [CrossRef] [PubMed]
- Jang, H.S.; Shin, W.J.; Lee, J.E.; Do, J.T. Cpg and non-cpg methylation in epigenetic gene regulation and brain function. Genes 2017, 8. [Google Scholar]
- Allis, C.D.; Jenuwein, T. The molecular hallmarks of epigenetic control. Nat. Rev. Genet. 2016, 17, 487–500. [Google Scholar] [CrossRef] [PubMed]
- Portela, A.; Esteller, M. Epigenetic modifications and human disease. Nat. Biotechnol. 2010, 28, 1057–1068. [Google Scholar] [CrossRef] [PubMed]
- Biswas, S.; Rao, C.M. Epigenetics in cancer: Fundamentals and beyond. Pharmacol. Ther. 2017, 173, 118–134. [Google Scholar] [CrossRef] [PubMed]
- Edwards, J.R.; Yarychkivska, O.; Boulard, M.; Bestor, T.H. DNA methylation and DNA methyltransferases. Epigenetics Chromatin 2017, 10, 23. [Google Scholar] [CrossRef]
- Aran, D.; Toperoff, G.; Rosenberg, M.; Hellman, A. Replication timing-related and gene body-specific methylation of active human genes. Hum. Mol. Genet. 2011, 20, 670–680. [Google Scholar] [CrossRef]
- Aran, D.; Sabato, S.; Hellman, A. DNA methylation of distal regulatory sites characterizes dysregulation of cancer genes. Genome Biol. 2013, 14, R21. [Google Scholar] [CrossRef]
- Yang, X.; Han, H.; De Carvalho, D.D.; Lay, F.D.; Jones, P.A.; Liang, G. Gene body methylation can alter gene expression and is a therapeutic target in cancer. Cancer Cell 2014, 26, 577–590. [Google Scholar] [CrossRef]
- Jurkowska, R.Z.; Ceccaldi, A.; Zhang, Y.; Arimondo, P.B.; Jeltsch, A. DNA methyltransferase assays. Methods Mol. Biol. 2011, 791, 157–177. [Google Scholar] [PubMed]
- Merlo, A.; Herman, J.G.; Mao, L.; Lee, D.J.; Gabrielson, E.; Burger, P.C.; Baylin, S.B.; Sidransky, D. 5′ cpg island methylation is associated with transcriptional silencing of the tumour suppressor p16/cdkn2/mts1 in human cancers. Nat. Med. 1995, 1, 686–692. [Google Scholar] [CrossRef] [PubMed]
- Pei, J.H.; Luo, S.Q.; Zhong, Y.; Chen, J.H.; Xiao, H.W.; Hu, W.X. The association between non-hodgkin lymphoma and methylation of p73. Tumour Biol. J. Int. Soc. Oncodev. Biol. Med. 2011, 32, 1133–1138. [Google Scholar] [CrossRef] [PubMed]
- Stefansson, O.A.; Jonasson, J.G.; Olafsdottir, K.; Hilmarsdottir, H.; Olafsdottir, G.; Esteller, M.; Johannsson, O.T.; Eyfjord, J.E. CpG island hypermethylation of BRCA1 and loss of prb as co-occurring events in basal/triple-negative breast cancer. Epigenetics 2011, 6, 638–649. [Google Scholar] [CrossRef]
- Guan, Z.; Zhang, J.; Song, S.; Dai, D. Promoter methylation and expression of TIMP3 gene in gastric cancer. Diagn. Pathol. 2013, 8, 110. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rodriguez, J.; Frigola, J.; Vendrell, E.; Risques, R.A.; Fraga, M.F.; Morales, C.; Moreno, V.; Esteller, M.; Capella, G.; Ribas, M.; et al. Chromosomal instability correlates with genome-wide DNA demethylation in human primary colorectal cancers. Cancer Res. 2006, 66, 8462–9468. [Google Scholar] [CrossRef] [PubMed]
- Dawson, M.A.; Kouzarides, T. Cancer epigenetics: From mechanism to therapy. Cell 2012, 150, 12–27. [Google Scholar] [CrossRef] [PubMed]
- Hervouet, E.; Lalier, L.; Debien, E.; Cheray, M.; Geairon, A.; Rogniaux, H.; Loussouarn, D.; Martin, S.A.; Vallette, F.M.; Cartron, P.F. Disruption of Dnmt1/PCNA/UHRF1 interactions promotes tumorigenesis from human and mice glial cells. PLoS ONE 2010, 5, e11333. [Google Scholar] [CrossRef]
- Pacaud, R.; Brocard, E.; Lalier, L.; Hervouet, E.; Vallette, F.M.; Cartron, P.F. The Dnmt1/PCNA/UHRF1 disruption induces tumorigenesis characterized by similar genetic and epigenetic signatures. Sci. Rep. 2014, 4, 4230. [Google Scholar] [CrossRef] [PubMed]
- Nestor, C.E.; Ottaviano, R.; Reinhardt, D.; Cruickshanks, H.A.; Mjoseng, H.K.; McPherson, R.C.; Lentini, A.; Thomson, J.P.; Dunican, D.S.; Pennings, S.; et al. Rapid reprogramming of epigenetic and transcriptional profiles in mammalian culture systems. Genome Biol. 2015, 16, 11. [Google Scholar] [CrossRef] [Green Version]
- Hopfner, R.; Mousli, M.; Garnier, J.M.; Redon, R.; du Manoir, S.; Chatton, B.; Ghyselinck, N.; Oudet, P.; Bronner, C. Genomic structure and chromosomal mapping of the gene coding for ICBP90, a protein involved in the regulation of the topoisomerase iialpha gene expression. Gene 2001, 266, 15–23. [Google Scholar] [CrossRef]
- Hopfner, R.; Mousli, M.; Jeltsch, J.M.; Voulgaris, A.; Lutz, Y.; Marin, C.; Bellocq, J.P.; Oudet, P.; Bronner, C. ICBP90, a novel human ccaat binding protein, involved in the regulation of topoisomerase IIα expression. Cancer Res. 2000, 60, 121–128. [Google Scholar] [PubMed]
- Fagerberg, L.; Hallstrom, B.M.; Oksvold, P.; Kampf, C.; Djureinovic, D.; Odeberg, J.; Habuka, M.; Tahmasebpoor, S.; Danielsson, A.; Edlund, K.; et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol. Cell. Proteom. MCP 2014, 13, 397–406. [Google Scholar] [CrossRef] [PubMed]
- Bostick, M.; Kim, J.K.; Esteve, P.O.; Clark, A.; Pradhan, S.; Jacobsen, S.E. UHRF1 plays a role in maintaining DNA methylation in mammalian cells. Science 2007, 317, 1760–1764. [Google Scholar] [CrossRef]
- Sharif, J.; Muto, M.; Takebayashi, S.; Suetake, I.; Iwamatsu, A.; Endo, T.A.; Shinga, J.; Mizutani-Koseki, Y.; Toyoda, T.; Okamura, K.; et al. The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA. Nature 2007, 450, 908–912. [Google Scholar] [CrossRef] [PubMed]
- Li, E.; Bestor, T.H.; Jaenisch, R. Targeted mutation of the DNA methyltransferase gene results in embryonic lethality. Cell 1992, 69, 915–926. [Google Scholar] [CrossRef]
- Muto, M.; Kanari, Y.; Kubo, E.; Takabe, T.; Kurihara, T.; Fujimori, A.; Tatsumi, K. Targeted disruption of Np95 gene renders murine embryonic stem cells hypersensitive to DNA damaging agents and DNA replication blocks. J. Biol. Chem. 2002, 277, 34549–34555. [Google Scholar] [CrossRef]
- Hermann, A.; Gowher, H.; Jeltsch, A. Biochemistry and biology of mammalian DNA methyltransferases. Cell. Mol. Life Sci. CMLS 2004, 61, 2571–2587. [Google Scholar] [CrossRef]
- Alhosin, M.; Sharif, T.; Mousli, M.; Etienne-Selloum, N.; Fuhrmann, G.; Schini-Kerth, V.B.; Bronner, C. Down-regulation of UHRF1, associated with re-expression of tumor suppressor genes, is a common feature of natural compounds exhibiting anti-cancer properties. J. Exp. Clin. Cancer Res. 2011, 30, 41. [Google Scholar] [CrossRef] [Green Version]
- Mohan, K.N.; Chaillet, J.R. Cell and molecular biology of DNA methyltransferase 1. Int. Rev. Cell Mol. Biol. 2013, 306, 1–42. [Google Scholar]
- Jurkowska, R.Z.; Jeltsch, A. Enzymology of mammalian DNA methyltransferases. Adv. Exp. Med. Biol. 2016, 945, 87–122. [Google Scholar] [PubMed]
- Choudhry, H.; Zamzami, M.A.; Omran, Z.; Wu, W.; Mousli, M.; Bronner, C.; Alhosin, M. Targeting microRNA/UHRF1 pathways as a novel strategy for cancer therapy. Oncol. Lett. 2018, 15, 3–10. [Google Scholar] [CrossRef] [PubMed]
- Gowher, H.; Jeltsch, A. Mammalian DNA methyltransferases: New discoveries and open questions. Biochem. Soc. Trans. 2018, 46, 1191–1202. [Google Scholar] [CrossRef] [PubMed]
- Ashraf, W.; Ibrahim, A.; Alhosin, M.; Zaayter, L.; Ouararhni, K.; Papin, C.; Ahmad, T.; Hamiche, A.; Mely, Y.; Bronner, C.; et al. The epigenetic integrator uhrf1: On the road to become a universal biomarker for cancer. Oncotarget 2017, 8, 51946–51962. [Google Scholar] [CrossRef] [PubMed]
- Alhosin, M.; Omran, Z.; Zamzami, M.A.; Al-Malki, A.L.; Choudhry, H.; Mousli, M.; Bronner, C. Signalling pathways in UHRF1-dependent regulation of tumor suppressor genes in cancer. J. Exp. Clin. Cancer Res. 2016, 35, 174. [Google Scholar] [CrossRef] [PubMed]
- Bronner, C.; Krifa, M.; Mousli, M. Increasing role of UHRF1 in the reading and inheritance of the epigenetic code as well as in tumorogenesis. Biochem Pharm. 2013, 86, 1643–1649. [Google Scholar] [CrossRef]
- Bronner, C. Control of dnmt1 abundance in epigenetic inheritance by acetylation, ubiquitylation, and the histone code. Sci. Signal. 2011, 4, pe3. [Google Scholar] [CrossRef]
- Sidhu, H.; Capalash, N. Uhrf1: The key regulator of epigenetics and molecular target for cancer therapeutics. Tumour Biol. J. Int. Soc. Oncodev. Biol. Med. 2017, 39, 1010428317692205. [Google Scholar] [CrossRef] [PubMed]
- Beck, A.; Trippel, F.; Wagner, A.; Joppien, S.; Felle, M.; Vokuhl, C.; Schwarzmayr, T.; Strom, T.M.; von Schweinitz, D.; Langst, G.; et al. Overexpression of UHRF1 promotes silencing of tumor suppressor genes and predicts outcome in hepatoblastoma. Clin. Epigenetics 2018, 10, 27. [Google Scholar] [CrossRef] [Green Version]
- Boukhari, A.; Alhosin, M.; Bronner, C.; Sagini, K.; Truchot, C.; Sick, E.; Schini-Kerth, V.B.; Andre, P.; Mely, Y.; Mousli, M.; et al. CD47 activation-induced UHRF1 over-expression is associated with silencing of tumor suppressor gene p16INK4a in glioblastoma cells. Anticancer Res. 2015, 35, 149–157. [Google Scholar]
- Krifa, M.; Alhosin, M.; Muller, C.D.; Gies, J.P.; Chekir-Ghedira, L.; Ghedira, K.; Mely, Y.; Bronner, C.; Mousli, M. Limoniastrum guyonianum aqueous gall extract induces apoptosis in human cervical cancer cells involving p16INK4a re-expression related to UHRF1 and Dnmt1 down-regulation. J. Exp. Clin. Cancer Res. 2013, 32, 30. [Google Scholar] [CrossRef] [PubMed]
- Achour, M.; Mousli, M.; Alhosin, M.; Ibrahim, A.; Peluso, J.; Muller, C.D.; Schini-Kerth, V.B.; Hamiche, A.; Dhe-Paganon, S.; Bronner, C. Epigallocatechin-3-gallate up-regulates tumor suppressor gene expression via a reactive oxygen species-dependent down-regulation of UHRF1. Biochem. Biophys. Res. Commun. 2013, 430, 208–212. [Google Scholar] [CrossRef] [PubMed]
- Sharif, T.; Alhosin, M.; Auger, C.; Minker, C.; Kim, J.H.; Etienne-Selloum, N.; Bories, P.; Gronemeyer, H.; Lobstein, A.; Bronner, C.; et al. Aronia melanocarpa juice induces a redox-sensitive p73-related caspase 3-dependent apoptosis in human leukemia cells. PLoS ONE 2012, 7, e32526. [Google Scholar] [CrossRef] [PubMed]
- Abusnina, A.; Keravis, T.; Yougbare, I.; Bronner, C.; Lugnier, C. Anti-proliferative effect of curcumin on melanoma cells is mediated by pde1a inhibition that regulates the epigenetic integrator UHRF1. Mol. Nutr. Food Res. 2011, 55, 1677–1689. [Google Scholar] [CrossRef]
- Abusnina, A.; Alhosin, M.; Keravis, T.; Muller, C.D.; Fuhrmann, G.; Bronner, C.; Lugnier, C. Down-regulation of cyclic nucleotide phosphodiesterase PDE1A is the key event of p73 and UHRF1 deregulation in thymoquinone-induced acute lymphoblastic leukemia cell apoptosis. Cell. Signal. 2011, 23, 152–160. [Google Scholar] [CrossRef]
- Zhang, Y.; Huang, Z.; Zhu, Z.; Zheng, X.; Liu, J.; Han, Z.; Ma, X.; Zhang, Y. Upregulated UHRF1 promotes bladder cancer cell invasion by epigenetic silencing of KiSS1. PLoS ONE 2014, 9, e104252. [Google Scholar] [CrossRef]
- Mousli, M.; Hopfner, R.; Abbady, A.Q.; Monte, D.; Jeanblanc, M.; Oudet, P.; Louis, B.; Bronner, C. ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells. Br. J. Cancer 2003, 89, 120–127. [Google Scholar] [CrossRef] [Green Version]
- Patnaik, D.; Esteve, P.O.; Pradhan, S. Targeting the set and ring-associated (SRA) domain of ubiquitin-like, phd and ring finger-containing 1 (UHRF1) for anti-cancer drug development. Oncotarget 2018, 9, 26243–26258. [Google Scholar] [CrossRef]
- Jia, Y.; Li, P.; Fang, L.; Zhu, H.; Xu, L.; Cheng, H.; Zhang, J.; Li, F.; Feng, Y.; Li, Y.; et al. Negative regulation of Dnmt3a de novo DNA methylation by frequently overexpressed uhrf family proteins as a mechanism for widespread DNA hypomethylation in cancer. Cell Discov. 2016, 2, 16007. [Google Scholar] [CrossRef]
- Chuang, L.S.; Ian, H.I.; Koh, T.W.; Ng, H.H.; Xu, G.; Li, B.F. Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1. Science 1997, 277, 1996–2000. [Google Scholar] [CrossRef]
- Leonhardt, H.; Page, A.W.; Weier, H.U.; Bestor, T.H. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell 1992, 71, 865–873. [Google Scholar] [CrossRef] [Green Version]
- Spada, F.; Haemmer, A.; Kuch, D.; Rothbauer, U.; Schermelleh, L.; Kremmer, E.; Carell, T.; Langst, G.; Leonhardt, H. Dnmt1 but not its interaction with the replication machinery is required for maintenance of DNA methylation in human cells. J. Cell Biol. 2007, 176, 565–571. [Google Scholar] [CrossRef] [PubMed]
- Schermelleh, L.; Haemmer, A.; Spada, F.; Rosing, N.; Meilinger, D.; Rothbauer, U.; Cardoso, M.C.; Leonhardt, H. Dynamics of Dnmt1 interaction with the replication machinery and its role in postreplicative maintenance of DNA methylation. Nucleic Acids Res. 2007, 35, 4301–4312. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Mudbhary, R.; Hoshida, Y.; Chernyavskaya, Y.; Jacob, V.; Villanueva, A.; Fiel, M.I.; Chen, X.; Kojima, K.; Thung, S.; Bronson, R.T.; et al. UHRF1 overexpression drives DNA hypomethylation and hepatocellular carcinoma. Cancer Cell 2014, 25, 196–209. [Google Scholar] [CrossRef]
- Fatemi, M.; Hermann, A.; Gowher, H.; Jeltsch, A. Dnmt3a and dnmt1 functionally cooperate during de novo methylation of DNA. Eur. J. Biochem. 2002, 269, 4981–4984. [Google Scholar] [CrossRef] [PubMed]
- Jair, K.W.; Bachman, K.E.; Suzuki, H.; Ting, A.H.; Rhee, I.; Yen, R.W.; Baylin, S.B.; Schuebel, K.E. De novo cpg island methylation in human cancer cells. Cancer Res. 2006, 66, 682–692. [Google Scholar] [CrossRef] [PubMed]
- Kilin, V.; Gavvala, K.; Barthes, N.P.; Michel, B.Y.; Shin, D.; Boudier, C.; Mauffret, O.; Yashchuk, V.; Mousli, M.; Ruff, M.; et al. Dynamics of methylated cytosine flipping by UHRF1. J. Am. Chem. Soc. 2017, 139, 2520–2528. [Google Scholar] [CrossRef]
- Greiner, V.J.; Kovalenko, L.; Humbert, N.; Richert, L.; Birck, C.; Ruff, M.; Zaporozhets, O.A.; Dhe-Paganon, S.; Bronner, C.; Mely, Y. Site-selective monitoring of the interaction of the sra domain of UHRF1 with target DNA sequences labeled with 2-aminopurine. Biochemistry 2015, 54, 6012–6020. [Google Scholar] [CrossRef]
- Bronner, C.; Fuhrmann, G.; Chedin, F.L.; Macaluso, M.; Dhe-Paganon, S. UHRF1 links the histone code and DNA methylation to ensure faithful epigenetic memory inheritance. Genet. Epigenetics 2010, 2009, 29–36. [Google Scholar] [CrossRef]
- Achour, M.; Jacq, X.; Ronde, P.; Alhosin, M.; Charlot, C.; Chataigneau, T.; Jeanblanc, M.; Macaluso, M.; Giordano, A.; Hughes, A.D.; et al. The interaction of the sra domain of ICBP90 with a novel domain of DNMT1 is involved in the regulation of VEGF gene expression. Oncogene 2008, 27, 2187–2197. [Google Scholar] [CrossRef]
- Avvakumov, G.V.; Walker, J.R.; Xue, S.; Li, Y.; Duan, S.; Bronner, C.; Arrowsmith, C.H.; Dhe-Paganon, S. Structural basis for recognition of hemi-methylated DNA by the SRA domain of human uhrf1. Nature 2008, 455, 822–825. [Google Scholar] [CrossRef] [PubMed]
- Ren, R.; Horton, J.R.; Zhang, X.; Blumenthal, R.M.; Cheng, X. Detecting and interpreting DNA methylation marks. Curr. Opin. Struct. Biol. 2018, 53, 88–99. [Google Scholar] [CrossRef] [PubMed]
- Tauber, M.; Fischle, W. Conserved linker regions and their regulation determine multiple chromatin-binding modes of UHRF1. Nucleus 2015, 6, 123–132. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Hashimoto, H.; Horton, J.R.; Zhang, X.; Bostick, M.; Jacobsen, S.E.; Cheng, X. The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix. Nature 2008, 455, 826–829. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Smets, M.; Link, S.; Wolf, P.; Schneider, K.; Solis, V.; Ryan, J.; Meilinger, D.; Qin, W.; Leonhardt, H. DNMT1 mutations found in HSANIE patients affect interaction with UHRF1 and neuronal differentiation. Hum. Mol. Genet. 2017, 26, 1522–1534. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jung, H.J.; Byun, H.O.; Jee, B.A.; Min, S.; Jeoun, U.W.; Lee, Y.K.; Seo, Y.; Woo, H.G.; Yoon, G. The ubiquitin-like with phd and ring finger domains 1 (UHRF1)/DNA methyltransferase 1 (DNMT1) axis is a primary regulator of cell senescence. J. Biol. Chem. 2017, 292, 3729–3739. [Google Scholar] [CrossRef] [PubMed]
- Sen, G.L.; Reuter, J.A.; Webster, D.E.; Zhu, L.; Khavari, P.A. DNMT1 maintains progenitor function in self-renewing somatic tissue. Nature 2010, 463, 563–567. [Google Scholar] [CrossRef] [Green Version]
- Blanchart, A.; Navis, A.C.; Assaife-Lopes, N.; Usoskin, D.; Aranda, S.; Sontheimer, J.; Ernfors, P. UHRF1 licensed self-renewal of active adult neural stem cells. Stem Cells 2018. [Google Scholar] [CrossRef]
- Zhao, J.; Chen, X.; Song, G.; Zhang, J.; Liu, H.; Liu, X. Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes. Proc. Natl. Acad. Sci. USA 2017, 114, E142–E151. [Google Scholar] [CrossRef]
- Murao, N.; Matsubara, S.; Matsuda, T.; Noguchi, H.; Mutoh, T.; Mutoh, M.; Koseki, H.; Namihira, M.; Nakashima, K. Np95/UHRF1 regulates tumor suppressor gene expression of neural stem/precursor cells, contributing to neurogenesis in the adult mouse brain. Neurosci. Res. 2018. [Google Scholar] [CrossRef]
- Chen, C.; Zhai, S.; Zhang, L.; Chen, J.; Long, X.; Qin, J.; Li, J.; Huo, R.; Wang, X. Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection. J. Exp. Med. 2018, 215, 1437–1448. [Google Scholar] [CrossRef] [PubMed]
- Obata, Y.; Furusawa, Y.; Endo, T.A.; Sharif, J.; Takahashi, D.; Atarashi, K.; Nakayama, M.; Onawa, S.; Fujimura, Y.; Takahashi, M.; et al. The epigenetic regulator uhrf1 facilitates the proliferation and maturation of colonic regulatory t cells. Nat. Immunol. 2014, 15, 571–579. [Google Scholar] [CrossRef] [PubMed]
- Elia, L.; Kunderfranco, P.; Carullo, P.; Vacchiano, M.; Farina, F.M.; Hall, I.F.; Mantero, S.; Panico, C.; Papait, R.; Condorelli, G.; et al. UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease. J. Clin. Investig. 2018, 128, 2473–2486. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Milagre, I.; Stubbs, T.M.; King, M.R.; Spindel, J.; Santos, F.; Krueger, F.; Bachman, M.; Segonds-Pichon, A.; Balasubramanian, S.; Andrews, S.R.; et al. Gender differences in global but not targeted demethylation in IPSC reprogramming. Cell Rep. 2017, 18, 1079–1089. [Google Scholar] [CrossRef] [PubMed]
- Yamashita, M.; Inoue, K.; Saeki, N.; Ideta-Otsuka, M.; Yanagihara, Y.; Sawada, Y.; Sakakibara, I.; Lee, J.; Ichikawa, K.; Kamei, Y.; et al. UHRF1 is indispensable for normal limb growth by regulating chondrocyte differentiation through specific gene expression. Development 2018, 145, dev157412. [Google Scholar] [CrossRef] [PubMed]
- Tittle, R.K.; Sze, R.; Ng, A.; Nuckels, R.J.; Swartz, M.E.; Anderson, R.M.; Bosch, J.; Stainier, D.Y.; Eberhart, J.K.; Gross, J.M. UHRF1 and DNMT1 are required for development and maintenance of the zebrafish lens. Dev. Biol. 2011, 350, 50–63. [Google Scholar] [CrossRef] [PubMed]
- Lydon-Rochelle, M.T.; Cardenas, V.; Nelson, J.L.; Tomashek, K.M.; Mueller, B.A.; Easterling, T.R. Validity of maternal and perinatal risk factors reported on fetal death certificates. Am. J. Public Health 2005, 95, 1948–1951. [Google Scholar] [CrossRef] [PubMed]
- Nady, N.; Lemak, A.; Walker, J.R.; Avvakumov, G.V.; Kareta, M.S.; Achour, M.; Xue, S.; Duan, S.; Allali-Hassani, A.; Zuo, X.; et al. Recognition of multivalent histone states associated with heterochromatin by UHRF1 protein. J. Biol. Chem. 2011, 286, 24300–24311. [Google Scholar] [CrossRef] [PubMed]
- Xie, S.; Jakoncic, J.; Qian, C. UHRF1 double tudor domain and the adjacent phd finger act together to recognize k9me3-containing histone H3 tail. J. Mol. Biol. 2012, 415, 318–328. [Google Scholar] [CrossRef]
- Du, J.; Johnson, L.M.; Jacobsen, S.E.; Patel, D.J. DNA methylation pathways and their crosstalk with histone methylation. Nat. Rev. Mol. Cell Biol. 2015, 16, 519–532. [Google Scholar] [CrossRef] [Green Version]
- Rothbart, S.B.; Krajewski, K.; Nady, N.; Tempel, W.; Xue, S.; Badeaux, A.I.; Barsyte-Lovejoy, D.; Martinez, J.Y.; Bedford, M.T.; Fuchs, S.M.; et al. Association of UHRF1 with methylated H3K9 directs the maintenance of DNA methylation. Nat. Struct. Mol. Biol. 2012, 19, 1155–1160. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Rothbart, S.B.; Dickson, B.M.; Ong, M.S.; Krajewski, K.; Houliston, S.; Kireev, D.B.; Arrowsmith, C.H.; Strahl, B.D. Multivalent histone engagement by the linked tandem tudor and phd domains of UHRF1 is required for the epigenetic inheritance of DNA methylation. Genes Dev. 2013, 27, 1288–1298. [Google Scholar] [CrossRef] [PubMed]
- Liu, X.; Gao, Q.; Li, P.; Zhao, Q.; Zhang, J.; Li, J.; Koseki, H.; Wong, J. UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated h3k9. Nat. Commun. 2013, 4, 1563. [Google Scholar] [CrossRef] [PubMed]
- Rajakumara, E.; Wang, Z.; Ma, H.; Hu, L.; Chen, H.; Lin, Y.; Guo, R.; Wu, F.; Li, H.; Lan, F.; et al. PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression. Mol. Cell 2011, 43, 275–284. [Google Scholar] [CrossRef] [PubMed]
- Lallous, N.; Legrand, P.; McEwen, A.G.; Ramon-Maiques, S.; Samama, J.P.; Birck, C. The PHD finger of human UHRF1 reveals a new subgroup of unmethylated histone H3 tail readers. PLoS ONE 2011, 6, e27599. [Google Scholar] [CrossRef] [PubMed]
- Hu, L.; Li, Z.; Wang, P.; Lin, Y.; Xu, Y. Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2. Cell Res. 2011, 21, 1374–1378. [Google Scholar] [CrossRef] [Green Version]
- Wang, C.; Shen, J.; Yang, Z.; Chen, P.; Zhao, B.; Hu, W.; Lan, W.; Tong, X.; Wu, H.; Li, G.; et al. Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger. Cell Res. 2011, 21, 1379–1382. [Google Scholar] [CrossRef] [Green Version]
- Qin, W.; Wolf, P.; Liu, N.; Link, S.; Smets, M.; La Mastra, F.; Forne, I.; Pichler, G.; Horl, D.; Fellinger, K.; et al. DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination. Cell Res. 2015, 25, 911–929. [Google Scholar] [CrossRef] [Green Version]
- Ronau, J.A.; Beckmann, J.F.; Hochstrasser, M. Substrate specificity of the ubiquitin and Ubl proteases. Cell Res. 2016, 26, 441–456. [Google Scholar] [CrossRef] [Green Version]
- DaRosa, P.A.; Harrison, J.S.; Zelter, A.; Davis, T.N.; Brzovic, P.; Kuhlman, B.; Klevit, R.E. A bifunctional role for the UHRF1 Ubl domain in the control of hemi-methylated DNA-dependent histone ubiquitylation. Mol. Cell 2018, 72, 753.e6–765.e6. [Google Scholar] [CrossRef]
- Foster, B.M.; Stolz, P.; Mulholland, C.B.; Montoya, A.; Kramer, H.; Bultmann, S.; Bartke, T. Critical role of the UBL domain in stimulating the E3 ubiquitin ligase activity of uhrf1 toward chromatin. Mol. Cell 2018, 72, 739.e9–752.e9. [Google Scholar] [CrossRef] [PubMed]
- Leonhardt, H.; Cardoso, M.C. DNA methylation, nuclear structure, gene expression and cancer. J. Cell. Biochem. Suppl. 2000, 79 (Suppl. 35), 78–83. [Google Scholar] [CrossRef]
- Qin, W.; Leonhardt, H.; Pichler, G. Regulation of DNA methyltransferase 1 by interactions and modifications. Nucleus 2011, 2, 392–402. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jeltsch, A.; Jurkowska, R.Z. New concepts in DNA methylation. Trends Biochem. Sci. 2014, 39, 310–318. [Google Scholar] [CrossRef] [PubMed]
- Jeltsch, A.; Jurkowska, R.Z. Allosteric control of mammalian DNA methyltransferases—A new regulatory paradigm. Nucleic Acids Res. 2016, 44, 8556–8575. [Google Scholar] [CrossRef] [PubMed]
- Zhang, Z.M.; Liu, S.; Lin, K.; Luo, Y.; Perry, J.J.; Wang, Y.; Song, J. Crystal structure of human DNA methyltransferase 1. J. Mol. Biol. 2015, 427, 2520–2531. [Google Scholar] [CrossRef] [PubMed]
- Fang, J.; Cheng, J.; Wang, J.; Zhang, Q.; Liu, M.; Gong, R.; Wang, P.; Zhang, X.; Feng, Y.; Lan, W.; et al. Hemi-methylated DNA opens a closed conformation of uhrf1 to facilitate its histone recognition. Nat. Commun. 2016, 7, 11197. [Google Scholar] [CrossRef] [PubMed]
- Gelato, K.A.; Tauber, M.; Ong, M.S.; Winter, S.; Hiragami-Hamada, K.; Sindlinger, J.; Lemak, A.; Bultsma, Y.; Houliston, S.; Schwarzer, D.; et al. Accessibility of different histone H3-binding domains of UHRF1 is allosterically regulated by phosphatidylinositol 5-phosphate. Mol. Cell 2014, 54, 905–919. [Google Scholar] [CrossRef]
- Gao, L.; Tan, X.F.; Zhang, S.; Wu, T.; Zhang, Z.M.; Ai, H.W.; Song, J. An intramolecular interaction of UHRF1 reveals dual control for its histone association. Structure 2018, 26, 304.e3–311.e3. [Google Scholar] [CrossRef] [PubMed]
- Misaki, T.; Yamaguchi, L.; Sun, J.; Orii, M.; Nishiyama, A.; Nakanishi, M. The replication foci targeting sequence (RFTS) of DNMT1 functions as a potent histone H3 binding domain regulated by autoinhibition. Biochem. Biophys. Res. Commun. 2016, 470, 741–747. [Google Scholar] [CrossRef]
- Nishiyama, A.; Yamaguchi, L.; Sharif, J.; Johmura, Y.; Kawamura, T.; Nakanishi, K.; Shimamura, S.; Arita, K.; Kodama, T.; Ishikawa, F.; et al. Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication. Nature 2013, 502, 249–253. [Google Scholar] [CrossRef] [PubMed]
- Ishiyama, S.; Nishiyama, A.; Saeki, Y.; Moritsugu, K.; Morimoto, D.; Yamaguchi, L.; Arai, N.; Matsumura, R.; Kawakami, T.; Mishima, Y.; et al. Structure of the dnmt1 reader module complexed with a unique two-mono-ubiquitin mark on histone H3 reveals the basis for DNA methylation maintenance. Mol. Cell 2017, 68, 350.e357–360.e357. [Google Scholar] [CrossRef] [PubMed]
- Harrison, J.S.; Cornett, E.M.; Goldfarb, D.; DaRosa, P.A.; Li, Z.M.; Yan, F.; Dickson, B.M.; Guo, A.H.; Cantu, D.V.; Kaustov, L.; et al. Hemi-methylated DNA regulates DNA methylation inheritance through allosteric activation of H3 ubiquitylation by UHRF1. eLife 2016, 5, e17101. [Google Scholar] [CrossRef] [PubMed]
- Jenkins, Y.; Markovtsov, V.; Lang, W.; Sharma, P.; Pearsall, D.; Warner, J.; Franci, C.; Huang, B.; Huang, J.; Yam, G.C.; et al. Critical role of the ubiquitin ligase activity of UHRF1, a nuclear ring finger protein, in tumor cell growth. Mol. Biol. Cell 2005, 16, 5621–5629. [Google Scholar] [CrossRef] [PubMed]
- Ibrahim, A.; Alhosin, M.; Papin, C.; Ouararhni, K.; Omran, Z.; Zamzami, M.A.; Al-Malki, A.L.; Choudhry, H.; Mely, Y.; Hamiche, A.; et al. Thymoquinone challenges UHRF1 to commit auto-ubiquitination: A key event for apoptosis induction in cancer cells. Oncotarget 2018, 9, 28599–28611. [Google Scholar] [CrossRef]
- Li, T.; Wang, L.; Du, Y.; Xie, S.; Yang, X.; Lian, F.; Zhou, Z.; Qian, C. Structural and mechanistic insights into uhrf1-mediated DNMT1 activation in the maintenance DNA methylation. Nucleic Acids Res. 2018, 46, 3218–3231. [Google Scholar] [CrossRef]
- Komander, D.; Rape, M. The ubiquitin code. Annu. Rev. Biochem. 2012, 81, 203–229. [Google Scholar] [CrossRef]
- Peterson, C.L.; Laniel, M.A. Histones and histone modifications. Curr. Biol. 2004, 14, R546–R551. [Google Scholar] [CrossRef]
- Yamaguchi, L.; Nishiyama, A.; Misaki, T.; Johmura, Y.; Ueda, J.; Arita, K.; Nagao, K.; Obuse, C.; Nakanishi, M. Usp7-dependent histone h3 deubiquitylation regulates maintenance of DNA methylation. Sci. Rep. 2017, 7, 55. [Google Scholar] [CrossRef]
- Felle, M.; Joppien, S.; Nemeth, A.; Diermeier, S.; Thalhammer, V.; Dobner, T.; Kremmer, E.; Kappler, R.; Langst, G. The usp7/dnmt1 complex stimulates the DNA methylation activity of DNMT1 and regulates the stability of UHRF1. Nucleic Acids Res. 2011, 39, 8355–8365. [Google Scholar] [CrossRef]
- Bronner, C.; Achour, M.; Arima, Y.; Chataigneau, T.; Saya, H.; Schini-Kerth, V.B. The UHRF family: Oncogenes that are drugable targets for cancer therapy in the near future? Pharmacol. Ther. 2007, 115, 419–434. [Google Scholar] [CrossRef]
- Takeshita, K.; Suetake, I.; Yamashita, E.; Suga, M.; Narita, H.; Nakagawa, A.; Tajima, S. Structural insight into maintenance methylation by mouse DNA methyltransferase 1 (DNMT1). Proc. Natl. Acad. Sci. USA 2011, 108, 9055–9059. [Google Scholar] [CrossRef] [PubMed]
- Syeda, F.; Fagan, R.L.; Wean, M.; Avvakumov, G.V.; Walker, J.R.; Xue, S.; Dhe-Paganon, S.; Brenner, C. The replication focus targeting sequence (RFTS) domain is a DNA-competitive inhibitor of DNMT1. J. Biol. Chem. 2011, 286, 15344–15351. [Google Scholar] [CrossRef] [PubMed]
- Berkyurek, A.C.; Suetake, I.; Arita, K.; Takeshita, K.; Nakagawa, A.; Shirakawa, M.; Tajima, S. The DNA methyltransferase DNMT1 directly interacts with the set and ring finger-associated (SRA) domain of the multifunctional protein UHRF1 to facilitate accession of the catalytic center to hemi-methylated DNA. J. Biol. Chem. 2014, 289, 379–386. [Google Scholar] [CrossRef] [PubMed]
- Pichler, G.; Wolf, P.; Schmidt, C.S.; Meilinger, D.; Schneider, K.; Frauer, C.; Fellinger, K.; Rottach, A.; Leonhardt, H. Cooperative DNA and histone binding by UHRF2 links the two major repressive epigenetic pathways. J. Cell. Biochem. 2011, 112, 2585–2593. [Google Scholar] [CrossRef] [PubMed]
- Zhang, J.; Gao, Q.; Li, P.; Liu, X.; Jia, Y.; Wu, W.; Li, J.; Dong, S.; Koseki, H.; Wong, J. S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance. Cell Res. 2011, 21, 1723–1739. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Bashtrykov, P.; Jankevicius, G.; Jurkowska, R.Z.; Ragozin, S.; Jeltsch, A. The uhrf1 protein stimulates the activity and specificity of the maintenance DNA methyltransferase DNMT1 by an allosteric mechanism. J. Biol. Chem. 2014, 289, 4106–4115. [Google Scholar] [CrossRef]
- Vaughan, R.M.; Dickson, B.M.; Whelihan, M.F.; Johnstone, A.L.; Cornett, E.M.; Cheek, M.A.; Ausherman, C.A.; Cowles, M.W.; Sun, Z.W.; Rothbart, S.B. Chromatin structure and its chemical modifications regulate the ubiquitin ligase substrate selectivity of UHRF1. Proc. Natl. Acad. Sci. USA 2018, 115, 8775–8780. [Google Scholar] [CrossRef]
- Arita, K.; Ariyoshi, M.; Tochio, H.; Nakamura, Y.; Shirakawa, M. Recognition of hemi-methylated DNA by the sra protein UHRF1 by a base-flipping mechanism. Nature 2008, 455, 818–821. [Google Scholar] [CrossRef] [PubMed]
- Ferry, L.; Fournier, A.; Tsusaka, T.; Adelmant, G.; Shimazu, T.; Matano, S.; Kirsh, O.; Amouroux, R.; Dohmae, N.; Suzuki, T.; et al. Methylation of DNA ligase 1 by G9A/GLP recruits UHRF1 to replicating DNA and regulates DNA methylation. Mol. Cell 2017, 67, 550.e5–565.e5. [Google Scholar] [CrossRef]
- Miura, M.; Watanabe, H.; Sasaki, T.; Tatsumi, K.; Muto, M. Dynamic changes in subnuclear Np95 location during the cell cycle and its spatial relationship with DNA replication foci. Exp. Cell Res. 2001, 263, 202–208. [Google Scholar] [CrossRef] [PubMed]
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Bronner, C.; Alhosin, M.; Hamiche, A.; Mousli, M. Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns. Genes 2019, 10, 65. https://doi.org/10.3390/genes10010065
Bronner C, Alhosin M, Hamiche A, Mousli M. Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns. Genes. 2019; 10(1):65. https://doi.org/10.3390/genes10010065
Chicago/Turabian StyleBronner, Christian, Mahmoud Alhosin, Ali Hamiche, and Marc Mousli. 2019. "Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns" Genes 10, no. 1: 65. https://doi.org/10.3390/genes10010065