Journal Article
. 2011 Nov; 21(12):1723-39.
doi: 10.1038/cr.2011.176.

S phase-dependent interaction with DNMT1 dictates the role of UHRF1 but not UHRF2 in DNA methylation maintenance

Jiqin Zhang 1 Qinqin Gao  Pishun Li  Xiaoli Liu  Yuanhui Jia  Weicheng Wu  Jiwen Li  Shuo Dong  Haruhiko Koseki  Jiemin Wong  
Affiliations
  • PMID: 22064703
  •     38 References
  •     60 citations

Abstract

Recent studies demonstrate that UHRF1 is required for DNA methylation maintenance by targeting DNMT1 to DNA replication foci, presumably through its unique hemi-methylated DNA-binding activity and interaction with DNMT1. UHRF2, another member of the UHRF family proteins, is highly similar to UHRF1 in both sequence and structure, raising questions about its role in DNA methylation. In this study, we demonstrate that, like UHRF1, UHRF2 also binds preferentially to methylated histone H3 lysine 9 (H3K9) through its conserved tudor domain and hemi-methylated DNA through the SET and Ring associated domain. Like UHRF1, UHRF2 is enriched in pericentric heterochromatin. The heterochromatin localization depends to large extent on its methylated H3K9-binding activity and to less extent on its methylated DNA-binding activity. Coimmunoprecipitation experiments demonstrate that both UHRF1 and UHRF2 interact with DNMT1, DNMT3a, DNMT3b and G9a. Despite all these conserved functions, we find that UHRF2 is not able to rescue the DNA methylation defect in Uhrf1 null mouse embryonic stem cells. This can be attributed to the inability for UHRF2 to recruit DNMT1 to replication foci during S phase of the cell cycle. Indeed, we find that while UHRF1 interacts with DNMT1 in an S phase-dependent manner in cells, UHRF2 does not. Thus, our study demonstrates that UHRF2 and UHRF1 are not functionally redundant in DNA methylation maintenance and reveals the cell-cycle-dependent interaction between UHRF1 and DNMT1 as a key regulatory mechanism targeting DNMT1 for DNA methylation.

Establishing, maintaining and modifying DNA methylation patterns in plants and animals.
Julie A Law, Steven E Jacobsen.
Nat Rev Genet, 2010 Feb 10; 11(3). PMID: 20142834    Free PMC article.
Highly Cited. Review.
Methylation of histone H3 lysine 9 creates a binding site for HP1 proteins.
M Lachner, D O'Carroll, +2 authors, T Jenuwein.
Nature, 2001 Mar 10; 410(6824). PMID: 11242053
Highly Cited.
NIRF, a novel RING finger protein, is involved in cell-cycle regulation.
Tsutomu Mori, Yuanyuan Li, +2 authors, Hideo Kochi.
Biochem Biophys Res Commun, 2002 Aug 15; 296(3). PMID: 12176013
Accurate transcription initiation by RNA polymerase II in a soluble extract from isolated mammalian nuclei.
J D Dignam, R M Lebovitz, R G Roeder.
Nucleic Acids Res, 1983 Mar 11; 11(5). PMID: 6828386    Free PMC article.
Highly Cited.
Cooperative DNA and histone binding by Uhrf2 links the two major repressive epigenetic pathways.
Garwin Pichler, Patricia Wolf, +6 authors, Heinrich Leonhardt.
J Cell Biochem, 2011 May 21; 112(9). PMID: 21598301    Free PMC article.
The PHD domain of Np95 (mUHRF1) is involved in large-scale reorganization of pericentromeric heterochromatin.
Roberto Papait, Christian Pistore, +11 authors, Ian Marc Bonapace.
Mol Biol Cell, 2008 May 30; 19(8). PMID: 18508923    Free PMC article.
Selective recognition of methylated lysine 9 on histone H3 by the HP1 chromo domain.
A J Bannister, P Zegerman, +4 authors, T Kouzarides.
Nature, 2001 Mar 10; 410(6824). PMID: 11242054
Highly Cited.
Structure and function of eukaryotic DNA methyltransferases.
Taiping Chen, En Li.
Curr Top Dev Biol, 2004 Apr 20; 60. PMID: 15094296
Review.
A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei.
H Leonhardt, A W Page, H U Weier, T H Bestor.
Cell, 1992 Nov 27; 71(5). PMID: 1423634
Highly Cited.
The X-linked mental retardation gene PHF8 is a histone demethylase involved in neuronal differentiation.
Jihui Qiu, Guang Shi, +5 authors, Jiemin Wong.
Cell Res, 2010 Jun 16; 20(8). PMID: 20548336
Structural basis for site-specific reading of unmodified R2 of histone H3 tail by UHRF1 PHD finger.
Chengkun Wang, Jie Shen, +8 authors, Chunyang Cao.
Cell Res, 2011 Aug 03; 21(9). PMID: 21808299    Free PMC article.
NIRF is a ubiquitin ligase that is capable of ubiquitinating PCNP, a PEST-containing nuclear protein.
Tsutomu Mori, Yuanyuan Li, Hiroaki Hata, Hideo Kochi.
FEBS Lett, 2004 Jan 27; 557(1-3). PMID: 14741369
Crystal structure of PHD domain of UHRF1 and insights into recognition of unmodified histone H3 arginine residue 2.
Lulu Hu, Ze Li, +2 authors, Yanhui Xu.
Cell Res, 2011 Aug 03; 21(9). PMID: 21808300    Free PMC article.
Recognition of hemi-methylated DNA by the SRA protein UHRF1 by a base-flipping mechanism.
Kyohei Arita, Mariko Ariyoshi, +2 authors, Masahiro Shirakawa.
Nature, 2008 Sep 06; 455(7214). PMID: 18772891
Highly Cited.
ICBP90, an E2F-1 target, recruits HDAC1 and binds to methyl-CpG through its SRA domain.
Motoko Unoki, Toshihiko Nishidate, Yusuke Nakamura.
Oncogene, 2004 Sep 14; 23(46). PMID: 15361834
Highly Cited.
Temporal and spatial localization of novel nuclear protein NP95 in mitotic and meiotic cells.
T Uemura, E Kubo, +3 authors, M Muto.
Cell Struct Funct, 2000 Sep 13; 25(3). PMID: 10984098
The SRA protein Np95 mediates epigenetic inheritance by recruiting Dnmt1 to methylated DNA.
Jafar Sharif, Masahiro Muto, +11 authors, Haruhiko Koseki.
Nature, 2007 Nov 13; 450(7171). PMID: 17994007
Highly Cited.
Histone H3 lysine 4 methylation disrupts binding of nucleosome remodeling and deacetylase (NuRD) repressor complex.
Philip Zegerman, Benito Canas, Darryl Pappin, Tony Kouzarides.
J Biol Chem, 2002 Feb 19; 277(14). PMID: 11850414
ICBP90, a novel methyl K9 H3 binding protein linking protein ubiquitination with heterochromatin formation.
Panagiota Karagianni, Larbi Amazit, Jun Qin, Jiemin Wong.
Mol Cell Biol, 2007 Oct 31; 28(2). PMID: 17967883    Free PMC article.
Highly Cited.
Structural insights into a novel histone demethylase PHF8.
Lin Yu, Yang Wang, +8 authors, Zhongzhou Chen.
Cell Res, 2010 Jan 27; 20(2). PMID: 20101266
Set9, a novel histone H3 methyltransferase that facilitates transcription by precluding histone tail modifications required for heterochromatin formation.
Kenichi Nishioka, Sergei Chuikov, +4 authors, Danny Reinberg.
Genes Dev, 2002 Feb 19; 16(4). PMID: 11850410    Free PMC article.
Highly Cited.
DNA methylation and cancer.
Phillippa C Taberlay, Peter A Jones.
Prog Drug Res, 2010 Dec 15; 67. PMID: 21141722
Review.
Conservation and divergence of methylation patterning in plants and animals.
Suhua Feng, Shawn J Cokus, +12 authors, Steven E Jacobsen.
Proc Natl Acad Sci U S A, 2010 Apr 17; 107(19). PMID: 20395551    Free PMC article.
Highly Cited.
UHRF1 binds G9a and participates in p21 transcriptional regulation in mammalian cells.
Jong Kyong Kim, Pierre-Olivier Estève, Steven E Jacobsen, Sriharsa Pradhan.
Nucleic Acids Res, 2008 Dec 06; 37(2). PMID: 19056828    Free PMC article.
Alteration of large-scale chromatin structure by estrogen receptor.
Anne C Nye, Ramji R Rajendran, +3 authors, Andrew S Belmont.
Mol Cell Biol, 2002 Apr 25; 22(10). PMID: 11971975    Free PMC article.
Cloning and mapping of Np95 gene which encodes a novel nuclear protein associated with cell proliferation.
A Fujimori, Y Matsuda, +7 authors, M Muto.
Mamm Genome, 1999 Jan 09; 9(12). PMID: 9880673
Np95 interacts with de novo DNA methyltransferases, Dnmt3a and Dnmt3b, and mediates epigenetic silencing of the viral CMV promoter in embryonic stem cells.
Daniela Meilinger, Karin Fellinger, +5 authors, Heinrich Leonhardt.
EMBO Rep, 2009 Oct 03; 10(11). PMID: 19798101    Free PMC article.
ICBP90 belongs to a new family of proteins with an expression that is deregulated in cancer cells.
M Mousli, R Hopfner, +5 authors, C Bronner.
Br J Cancer, 2003 Jul 03; 89(1). PMID: 12838312    Free PMC article.
The SRA domain of UHRF1 flips 5-methylcytosine out of the DNA helix.
Hideharu Hashimoto, John R Horton, +3 authors, Xiaodong Cheng.
Nature, 2008 Sep 06; 455(7214). PMID: 18772888    Free PMC article.
Highly Cited.
Human DNA-(cytosine-5) methyltransferase-PCNA complex as a target for p21WAF1.
L S Chuang, H I Ian, +3 authors, B F Li.
Science, 1997 Sep 26; 277(5334). PMID: 9302295
Highly Cited.
Recognition of multivalent histone states associated with heterochromatin by UHRF1 protein.
Nataliya Nady, Alexander Lemak, +12 authors, Sirano Dhe-Paganon.
J Biol Chem, 2011 Apr 15; 286(27). PMID: 21489993    Free PMC article.
Multiple domains are involved in the targeting of the mouse DNA methyltransferase to the DNA replication foci.
Y Liu, E J Oakeley, L Sun, J P Jost.
Nucleic Acids Res, 1998 Mar 21; 26(4). PMID: 9461465    Free PMC article.
VIM1, a methylcytosine-binding protein required for centromeric heterochromatinization.
Hye Ryun Woo, Olga Pontes, Craig S Pikaard, Eric J Richards.
Genes Dev, 2007 Jan 24; 21(3). PMID: 17242155    Free PMC article.
UHRF1 plays a role in maintaining DNA methylation in mammalian cells.
Magnolia Bostick, Jong Kyong Kim, +3 authors, Steven E Jacobsen.
Science, 2007 Aug 04; 317(5845). PMID: 17673620
Highly Cited.
ICBP90, a novel human CCAAT binding protein, involved in the regulation of topoisomerase IIalpha expression.
R Hopfner, M Mousli, +6 authors, C Bronner.
Cancer Res, 2000 Jan 26; 60(1). PMID: 10646863
PHD finger recognition of unmodified histone H3R2 links UHRF1 to regulation of euchromatic gene expression.
Eerappa Rajakumara, Zhentian Wang, +11 authors, Yang Shi.
Mol Cell, 2011 Jul 23; 43(2). PMID: 21777816    Free PMC article.
Highly Cited.
The multi-domain protein Np95 connects DNA methylation and histone modification.
Andrea Rottach, Carina Frauer, +3 authors, Heinrich Leonhardt.
Nucleic Acids Res, 2009 Dec 23; 38(6). PMID: 20026581    Free PMC article.
Structural basis for recognition of hemi-methylated DNA by the SRA domain of human UHRF1.
George V Avvakumov, John R Walker, +5 authors, Sirano Dhe-Paganon.
Nature, 2008 Sep 06; 455(7214). PMID: 18772889
Highly Cited.
A novel histone H4 arginine 3 methylation-sensitive histone H4 binding activity and transcriptional regulatory function for signal recognition particle subunits SRP68 and SRP72.
Jingjing Li, Fan Zhou, +7 authors, Jiemin Wong.
J Biol Chem, 2012 Oct 11; 287(48). PMID: 23048028    Free PMC article.
Structural insight into coordinated recognition of trimethylated histone H3 lysine 9 (H3K9me3) by the plant homeodomain (PHD) and tandem tudor domain (TTD) of UHRF1 (ubiquitin-like, containing PHD and RING finger domains, 1) protein.
Jingdong Cheng, Yi Yang, +7 authors, Yanhui Xu.
J Biol Chem, 2012 Nov 20; 288(2). PMID: 23161542    Free PMC article.
UHRF2, a ubiquitin E3 ligase, acts as a small ubiquitin-like modifier E3 ligase for zinc finger protein 131.
Yohan Oh, Kwang Chul Chung.
J Biol Chem, 2013 Feb 14; 288(13). PMID: 23404503    Free PMC article.
UHRF1 targets DNMT1 for DNA methylation through cooperative binding of hemi-methylated DNA and methylated H3K9.
Xiaoli Liu, Qinqin Gao, +5 authors, Jiemin Wong.
Nat Commun, 2013 Mar 07; 4. PMID: 23463006
Highly Cited.
The nuclear protein UHRF2 is a direct target of the transcription factor E2F1 in the induction of apoptosis.
Huarui Lu, Timothy C Hallstrom.
J Biol Chem, 2013 Jul 09; 288(33). PMID: 23833190    Free PMC article.
Epigenetic regulation of autophagy by the methyltransferase G9a.
Amaia Artal-Martinez de Narvajas, Timothy S Gomez, +11 authors, Daniel D Billadeau.
Mol Cell Biol, 2013 Aug 07; 33(20). PMID: 23918802    Free PMC article.
Highly Cited.
Epidermal stem cells and their epigenetic regulation.
Qi Shen, Hongchuan Jin, Xian Wang.
Int J Mol Sci, 2013 Sep 04; 14(9). PMID: 23999591    Free PMC article.
Review.
Green tea polyphenol epigallocatechin 3-gallate, contributes to the degradation of DNMT3A and HDAC3 in HCT 116 human colon cancer cells.
Vondina R Moseley, Jay Morris, Rebecca W Knackstedt, Michael J Wargovich.
Anticancer Res, 2013 Dec 11; 33(12). PMID: 24324066    Free PMC article.
E2F1 coregulates cell cycle genes and chromatin components during the transition of oligodendrocyte progenitors from proliferation to differentiation.
Laura Magri, Victoria A Swiss, +7 authors, Patrizia Casaccia.
J Neurosci, 2014 Jan 24; 34(4). PMID: 24453336    Free PMC article.
Histone-binding domains: strategies for discovery and characterization.
Alex W Wilkinson, Or Gozani.
Biochim Biophys Acta, 2014 Feb 15; 1839(8). PMID: 24525102    Free PMC article.
Review.
Understanding the relationship between DNA methylation and histone lysine methylation.
Nathan R Rose, Robert J Klose.
Biochim Biophys Acta, 2014 Feb 25; 1839(12). PMID: 24560929    Free PMC article.
Highly Cited. Review.
Interpreting the language of histone and DNA modifications.
Scott B Rothbart, Brian D Strahl.
Biochim Biophys Acta, 2014 Mar 19; 1839(8). PMID: 24631868    Free PMC article.
Highly Cited. Review.
Identification of protein complexes that bind to histone H3 combinatorial modifications using super-SILAC and weighted correlation network analysis.
Natalia Kunowska, Maxime Rotival, +2 authors, Niall Dillon.
Nucleic Acids Res, 2015 Jan 22; 43(3). PMID: 25605797    Free PMC article.
Non-germ Line Restoration of Genomic Imprinting for a Small Subset of Imprinted Genes in Ubiquitin-like PHD and RING Finger Domain-Containing 1 (Uhrf1) Null Mouse Embryonic Stem Cells.
Shankang Qi, Zhiqiang Wang, +4 authors, Jiemin Wong.
J Biol Chem, 2015 Apr 23; 290(22). PMID: 25900245    Free PMC article.
DNA methylation requires a DNMT1 ubiquitin interacting motif (UIM) and histone ubiquitination.
Weihua Qin, Patricia Wolf, +12 authors, Heinrich Leonhardt.
Cell Res, 2015 Jun 13; 25(8). PMID: 26065575    Free PMC article.
Highly Cited.
Post-transcriptional gene silencing, transcriptional gene silencing and human immunodeficiency virus.
Catalina Méndez, Chantelle L Ahlenstiel, Anthony D Kelleher.
World J Virol, 2015 Aug 19; 4(3). PMID: 26279984    Free PMC article.
Review.
Novel Function of Lysine Methyltransferase G9a in the Regulation of Sox2 Protein Stability.
Jae-Young Lee, Se-Hwan Lee, +5 authors, Kyung-Soon Park.
PLoS One, 2015 Oct 23; 10(10). PMID: 26492085    Free PMC article.
Hemi-methylated DNA opens a closed conformation of UHRF1 to facilitate its histone recognition.
Jian Fang, Jingdong Cheng, +13 authors, Yanhui Xu.
Nat Commun, 2016 Apr 06; 7. PMID: 27045799    Free PMC article.
Multidimensional Proteomics Reveals a Role of UHRF2 in the Regulation of Epithelial-Mesenchymal Transition (EMT).
Mi Lai, Lizhu Liang, +9 authors, Jun Qin.
Mol Cell Proteomics, 2016 Apr 27; 15(7). PMID: 27114453    Free PMC article.
Upregulation of P53 promoted G1 arrest and apoptosis in human umbilical cord vein endothelial cells from preeclampsia.
Qinqin Gao, Xiaolin Zhu, +3 authors, Zhice Xu.
J Hypertens, 2016 Apr 27; 34(7). PMID: 27115339    Free PMC article.
Zinc Finger Protein 618 Regulates the Function of UHRF2 (Ubiquitin-like with PHD and Ring Finger Domains 2) as a Specific 5-Hydroxymethylcytosine Reader.
Yidan Liu, Bin Zhang, +3 authors, Xiaochun Yu.
J Biol Chem, 2016 Apr 30; 291(26). PMID: 27129234    Free PMC article.
Concerted changes in transcriptional regulation of genes involved in DNA methylation, demethylation, and folate-mediated one-carbon metabolism pathways in the NCI-60 cancer cell line panel in response to cancer drug treatment.
Julia Krushkal, Yingdong Zhao, +3 authors, Richard Simon.
Clin Epigenetics, 2016 Jun 28; 8. PMID: 27347216    Free PMC article.
Modifiers and Readers of DNA Modifications and Their Impact on Genome Structure, Expression, and Stability in Disease.
Anne K Ludwig, Peng Zhang, M C Cardoso.
Front Genet, 2016 Jul 23; 7. PMID: 27446199    Free PMC article.
Review.
The interplay between the lysine demethylase KDM1A and DNA methyltransferases in cancer cells is cell cycle dependent.
Carmen Brenner, Judith Luciani, +9 authors, Rachel Deplus.
Oncotarget, 2016 Jul 28; 7(37). PMID: 27449289    Free PMC article.
Negative regulation of DNMT3A de novo DNA methylation by frequently overexpressed UHRF family proteins as a mechanism for widespread DNA hypomethylation in cancer.
Yuanhui Jia, Pishun Li, +17 authors, Jiemin Wong.
Cell Discov, 2016 Jul 28; 2. PMID: 27462454    Free PMC article.
Dissecting the precise role of H3K9 methylation in crosstalk with DNA maintenance methylation in mammals.
Qian Zhao, Jiqin Zhang, +13 authors, Jiemin Wong.
Nat Commun, 2016 Aug 25; 7. PMID: 27554592    Free PMC article.
Loss of UHRF2 expression is associated with human neoplasia, promoter hypermethylation, decreased 5-hydroxymethylcytosine, and high proliferative activity.
Huarui Lu, Sweta Bhoopatiraju, +7 authors, Timothy C Hallstrom.
Oncotarget, 2016 Oct 16; 7(46). PMID: 27738314    Free PMC article.
UHRF2 decreases H3K9ac expression by interacting with it through the PHD and SRA/YDG domain in HepG2 hepatocellular carcinoma cells.
Ting Zhang, Linglin Zhao, +5 authors, Changzhu Duan.
Int J Mol Med, 2016 Dec 23; 39(1). PMID: 28004105    Free PMC article.
The 5-Hydroxymethylcytosine (5hmC) Reader UHRF2 Is Required for Normal Levels of 5hmC in Mouse Adult Brain and Spatial Learning and Memory.
Ruoyu Chen, Qiao Zhang, +14 authors, Jiemin Wong.
J Biol Chem, 2017 Jan 25; 292(11). PMID: 28115522    Free PMC article.
UHRF2 regulates local 5-methylcytosine and suppresses spontaneous seizures.
Yidan Liu, Bin Zhang, +4 authors, Xiaochun Yu.
Epigenetics, 2017 Apr 14; 12(7). PMID: 28402695    Free PMC article.
A Tox21 Approach to Altered Epigenetic Landscapes: Assessing Epigenetic Toxicity Pathways Leading to Altered Gene Expression and Oncogenic Transformation In Vitro.
Craig L Parfett, Daniel Desaulniers.
Int J Mol Sci, 2017 Jun 08; 18(6). PMID: 28587163    Free PMC article.
Review.
Interaction of the epigenetic integrator UHRF1 with the MYST domain of TIP60 inside the cell.
Waseem Ashraf, Christian Bronner, +7 authors, Marc Mousli.
J Exp Clin Cancer Res, 2017 Dec 23; 36(1). PMID: 29268763    Free PMC article.
Overexpression of UHRF2 in intrahepatic cholangiocarcinoma and its clinical significance.
Rui Peng, Xiaoyong Huang, +3 authors, Dousheng Bai.
Onco Targets Ther, 2017 Dec 23; 10. PMID: 29270024    Free PMC article.
Comparative biochemical analysis of UHRF proteins reveals molecular mechanisms that uncouple UHRF2 from DNA methylation maintenance.
Robert M Vaughan, Bradley M Dickson, +3 authors, Scott B Rothbart.
Nucleic Acids Res, 2018 Mar 06; 46(9). PMID: 29506131    Free PMC article.
Novel method for DNA methylation analysis using high-performance liquid chromatography and its clinical application.
Takuya Yotani, Yuriko Yamada, +6 authors, Yae Kanai.
Cancer Sci, 2018 Mar 10; 109(5). PMID: 29520901    Free PMC article.
DNA Methylation and Adult Neurogenesis.
Emily M Jobe, Xinyu Zhao.
Brain Plast, 2018 May 17; 3(1). PMID: 29765857    Free PMC article.
Review.
Targeting the SET and RING-associated (SRA) domain of ubiquitin-like, PHD and ring finger-containing 1 (UHRF1) for anti-cancer drug development.
Debasis Patnaik, Pierre-Olivier Estève, Sriharsa Pradhan.
Oncotarget, 2018 Jun 15; 9(40). PMID: 29899856    Free PMC article.
Review.
Epigenetic Inheritance: Concepts, Mechanisms and Perspectives.
Irene Lacal, Rossella Ventura.
Front Mol Neurosci, 2018 Oct 17; 11. PMID: 30323739    Free PMC article.
Identification of UHRF2 as a novel DNA interstrand crosslink sensor protein.
Anna Motnenko, Chih-Chao Liang, +11 authors, Martin A Cohn.
PLoS Genet, 2018 Oct 20; 14(10). PMID: 30335751    Free PMC article.
A Bifunctional Role for the UHRF1 UBL Domain in the Control of Hemi-methylated DNA-Dependent Histone Ubiquitylation.
Paul A DaRosa, Joseph S Harrison, +4 authors, Rachel E Klevit.
Mol Cell, 2018 Nov 06; 72(4). PMID: 30392931    Free PMC article.
The finger loop of the SRA domain in the E3 ligase UHRF1 is a regulator of ubiquitin targeting and is required for the maintenance of DNA methylation.
Robert M Vaughan, Scott B Rothbart, Bradley M Dickson.
J Biol Chem, 2019 Sep 05; 294(43). PMID: 31481468    Free PMC article.
Hemimethylation of CpG dyads is characteristic of secondary DMRs associated with imprinted loci and correlates with 5-hydroxymethylcytosine at paternally methylated sequences.
Julianna Nechin, Emma Tunstall, +4 authors, Tamara L Davis.
Epigenetics Chromatin, 2019 Oct 19; 12(1). PMID: 31623686    Free PMC article.
Association of UHRF1 gene polymorphisms with oligospermia in Chinese males.
Weiqiang Zhu, Jing Du, +7 authors, Runsheng Li.
J Assist Reprod Genet, 2019 Dec 06; 36(12). PMID: 31802345    Free PMC article.
Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns.
Christian Bronner, Mahmoud Alhosin, Ali Hamiche, Marc Mousli.
Genes (Basel), 2019 Jan 24; 10(1). PMID: 30669400    Free PMC article.
Review.
AKT drives SOX2 overexpression and cancer cell stemness in esophageal cancer by protecting SOX2 from UBR5-mediated degradation.
Zhen Wang, Li Kang, +7 authors, Jiemin Wong.
Oncogene, 2019 Mar 22; 38(26). PMID: 30894683
Defining UHRF1 Domains that Support Maintenance of Human Colon Cancer DNA Methylation and Oncogenic Properties.
Xiangqian Kong, Jie Chen, +15 authors, Stephen B Baylin.
Cancer Cell, 2019 Apr 09; 35(4). PMID: 30956060    Free PMC article.
SET8 prevents excessive DNA methylation by methylation-mediated degradation of UHRF1 and DNMT1.
Huifang Zhang, Qinqin Gao, +11 authors, Jiemin Wong.
Nucleic Acids Res, 2019 Aug 11; 47(17). PMID: 31400111    Free PMC article.
Crystal structure of the EcoKMcrA N-terminal domain (NEco): recognition of modified cytosine bases without flipping.
Anton Slyvka, Evelina Zagorskaitė, +2 authors, Matthias Bochtler.
Nucleic Acids Res, 2019 Nov 15; 47(22). PMID: 31724709    Free PMC article.
DNA Methylation Readers and Cancer: Mechanistic and Therapeutic Applications.
Niaz Mahmood, Shafaat A Rabbani.
Front Oncol, 2019 Jun 28; 9. PMID: 31245293    Free PMC article.
Review.
The histone and non-histone methyllysine reader activities of the UHRF1 tandem Tudor domain are dispensable for the propagation of aberrant DNA methylation patterning in cancer cells.
Robert M Vaughan, Ariana Kupai, +13 authors, Scott B Rothbart.
Epigenetics Chromatin, 2020 Oct 25; 13(1). PMID: 33097091    Free PMC article.
Maintenance DNA methylation is essential for regulatory T cell development and stability of suppressive function.
Kathryn A Helmin, Luisa Morales-Nebreda, +9 authors, Benjamin D Singer.
J Clin Invest, 2020 Sep 09; 130(12). PMID: 32897881    Free PMC article.
A role for LSH in facilitating DNA methylation by DNMT1 through enhancing UHRF1 chromatin association.
Mengmeng Han, Jialun Li, +9 authors, Jiemin Wong.
Nucleic Acids Res, 2020 Nov 11; 48(21). PMID: 33170271    Free PMC article.
Discovery of small molecules targeting the tandem tudor domain of the epigenetic factor UHRF1 using fragment-based ligand discovery.
Lyra Chang, James Campbell, +15 authors, Damian W Young.
Sci Rep, 2021 Jan 15; 11(1). PMID: 33441849    Free PMC article.
Association of expression of epigenetic molecular factors with DNA methylation and sensitivity to chemotherapeutic agents in cancer cell lines.
Suleyman Vural, Alida Palmisano, +3 authors, Julia Krushkal.
Clin Epigenetics, 2021 Mar 08; 13(1). PMID: 33676569    Free PMC article.
Ubiquitin-Specific-Processing Protease 7 Regulates Female Germline Stem Cell Self-Renewal Through DNA Methylation.
Yongqiang Zhao, Xiaoyong Li, +4 authors, Ji Wu.
Stem Cell Rev Rep, 2020 Nov 06; 17(3). PMID: 33151468    Free PMC article.
Mutation-induced DNMT1 cleavage drives neurodegenerative disease.
Wencai Wang, Xingsen Zhao, +7 authors, Jiemin Wong.
Sci Adv, 2021 Sep 14; 7(36). PMID: 34516921    Free PMC article.
Evolution of CG Methylation Maintenance Machinery in Plants.
Louis Tirot, Pauline E Jullien, Mathieu Ingouff.
Epigenomes, 2021 Dec 31; 5(3). PMID: 34968368    Free PMC article.
Review.
High-Throughput-Methyl-Reading (HTMR) assay: a solution based on nucleotide methyl-binding proteins enables large-scale screening for DNA/RNA methyltransferases and demethylases.
Senhao Xiao, Siqi Guo, +14 authors, Shijie Chen.
Nucleic Acids Res, 2021 Nov 01; 50(2). PMID: 34718755    Free PMC article.
Dppa3 facilitates self-renewal of embryonic stem cells by stabilization of pluripotent factors.
Shuang Zhao, Chuanyu Zhang, +6 authors, Na Liu.
Stem Cell Res Ther, 2022 Apr 29; 13(1). PMID: 35477484    Free PMC article.
UHRF2 regulates cell cycle, epigenetics and gene expression to control the timing of retinal progenitor and ganglion cell differentiation.
Xiaohong Wang, Aaron L Sarver, +6 authors, Timothy C Hallstrom.
Development, 2022 Mar 15; 149(6). PMID: 35285483    Free PMC article.