Imprint Stability and Plasticity During Development
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Transcriptional Modulator ZBED6 Affects Cell Cycle and Growth of Human Colorectal Cancer Cells
Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells Muhammad Akhtar Alia,1, Shady Younisb,c,1, Ola Wallermand, Rajesh Guptab, Leif Anderssonb,d,e,1,2, and Tobias Sjöbloma,1 aScience For Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden; bScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 85 Uppsala, Sweden; cDepartment of Animal Production, Ain Shams University, Shoubra El-Kheima, 11241 Cairo, Egypt; dDepartment of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden; and eDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843 Contributed by Leif Andersson, May 15, 2015 (sent for review December 10, 2014; reviewed by Jan-Ake Gustafsson) The transcription factor ZBED6 (zinc finger, BED-type containing 6) (QTN) with a large impact on body composition (muscle growth is a repressor of IGF2 whose action impacts development, cell pro- and fat deposition); mutant animals showed threefold higher IGF2 liferation, and growth in placental mammals. In human colorectal expression in postnatal muscle (11). ZBED6 was identified as the cancers, IGF2 overexpression is mutually exclusive with somatic nuclear factor specifically binding the wild-type IGF2 sequence but mutations in PI3K signaling components, providing genetic evi- not the mutated site. ChIP sequencing (ChIP-seq) in mouse C2C12 dence for a role in the PI3K pathway. To understand the role of cells identified more than 1,200 putative ZBED6 target genes, in- ZBED6 in tumorigenesis, we engineered and validated somatic cell cluding 262 genes encoding transcription factors (6). -
Cellular and Molecular Signatures in the Disease Tissue of Early
Cellular and Molecular Signatures in the Disease Tissue of Early Rheumatoid Arthritis Stratify Clinical Response to csDMARD-Therapy and Predict Radiographic Progression Frances Humby1,* Myles Lewis1,* Nandhini Ramamoorthi2, Jason Hackney3, Michael Barnes1, Michele Bombardieri1, Francesca Setiadi2, Stephen Kelly1, Fabiola Bene1, Maria di Cicco1, Sudeh Riahi1, Vidalba Rocher-Ros1, Nora Ng1, Ilias Lazorou1, Rebecca E. Hands1, Desiree van der Heijde4, Robert Landewé5, Annette van der Helm-van Mil4, Alberto Cauli6, Iain B. McInnes7, Christopher D. Buckley8, Ernest Choy9, Peter Taylor10, Michael J. Townsend2 & Costantino Pitzalis1 1Centre for Experimental Medicine and Rheumatology, William Harvey Research Institute, Barts and The London School of Medicine and Dentistry, Queen Mary University of London, Charterhouse Square, London EC1M 6BQ, UK. Departments of 2Biomarker Discovery OMNI, 3Bioinformatics and Computational Biology, Genentech Research and Early Development, South San Francisco, California 94080 USA 4Department of Rheumatology, Leiden University Medical Center, The Netherlands 5Department of Clinical Immunology & Rheumatology, Amsterdam Rheumatology & Immunology Center, Amsterdam, The Netherlands 6Rheumatology Unit, Department of Medical Sciences, Policlinico of the University of Cagliari, Cagliari, Italy 7Institute of Infection, Immunity and Inflammation, University of Glasgow, Glasgow G12 8TA, UK 8Rheumatology Research Group, Institute of Inflammation and Ageing (IIA), University of Birmingham, Birmingham B15 2WB, UK 9Institute of -
Ubiquitination/Deubiquitination and Acetylation/Deacetylation
Acta Pharmacologica Sinica (2011) 32: 139–140 npg © 2011 CPS and SIMM All rights reserved 1671-4083/11 $32.00 www.nature.com/aps Research Highlight Ubiquitination/deubiquitination and acetylation/ deacetylation: Making DNMT1 stability more coordinated Qi HONG, Zhi-ming SHAO* Acta Pharmacologica Sinica (2011) 32: 139–140; doi: 10.1038/aps.2011.3 n mammals, DNA methylation plays important role in human cancers[7, 8]. abundance of DNMT1 mutant lacking Ia crucial role in the regulation of Ubiquitinproteasome pathway is sig the HAUSP interaction domain, but not gene expression, telomere length, cell nificant in the stability of DNMT1[8], but the fulllength protein. These results differentiation, X chromosome inactiva ubiquitinmediated protein degradation show the coordination between ubiquit tion, genomic imprinting and tumori can be enhanced or attenuated by some ination of DNMT1 by UHRF1 and deu genesis[1]. DNA methylation patterns modifications like acetylation/deacety biquitination by HAUSP. Furthermore, are established de novo by DNA meth lation, protein methylation/demethyla they found that knockdown of HDAC1 yltransferases (DNMTs) 3a and 3b, tion, phosphorylation and Snitrosy increased DNMT1 acetylation, and whereas DNMT1 maintains the parent lation[9–11]. Estève et al demonstrated reduced DNMT1 abundance. Addition specific methylation from parental cells that SET7mediated lysine methy lation ally, acetyltransferase Tip60 which was to their progeny[2]. After DNA replica of DNMT1 decreased DNMT1 level found to acetylate DNMT1 promoted its tion, the new DNA strand is unmethy by ubiquitinmediated degradation[10]. ubiquitination, then destabilized it. At lated. Thus with the mother methylated Furthermore, an early study[12] showed last, Tip60 and HAUSP were found to strand, the DNA is hemimethylated. -
1 AGING Supplementary Table 2
SUPPLEMENTARY TABLES Supplementary Table 1. Details of the eight domain chains of KIAA0101. Serial IDENTITY MAX IN COMP- INTERFACE ID POSITION RESOLUTION EXPERIMENT TYPE number START STOP SCORE IDENTITY LEX WITH CAVITY A 4D2G_D 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ B 4D2G_E 52 - 69 52 69 100 100 2.65 Å PCNA X-RAY DIFFRACTION √ C 6EHT_D 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ D 6EHT_E 52 - 71 52 71 100 100 3.2Å PCNA X-RAY DIFFRACTION √ E 6GWS_D 41-72 41 72 100 100 3.2Å PCNA X-RAY DIFFRACTION √ F 6GWS_E 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ G 6GWS_F 41-72 41 72 100 100 2.9Å PCNA X-RAY DIFFRACTION √ H 6IIW_B 2-11 2 11 100 100 1.699Å UHRF1 X-RAY DIFFRACTION √ www.aging-us.com 1 AGING Supplementary Table 2. Significantly enriched gene ontology (GO) annotations (cellular components) of KIAA0101 in lung adenocarcinoma (LinkedOmics). Leading Description FDR Leading Edge Gene EdgeNum RAD51, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, CENPW, HJURP, NDC80, CDCA5, NCAPH, BUB1, ZWILCH, CENPK, KIF2C, AURKA, CENPN, TOP2A, CENPM, PLK1, ERCC6L, CDT1, CHEK1, SPAG5, CENPH, condensed 66 0 SPC24, NUP37, BLM, CENPE, BUB3, CDK2, FANCD2, CENPO, CENPF, BRCA1, DSN1, chromosome MKI67, NCAPG2, H2AFX, HMGB2, SUV39H1, CBX3, TUBG1, KNTC1, PPP1CC, SMC2, BANF1, NCAPD2, SKA2, NUP107, BRCA2, NUP85, ITGB3BP, SYCE2, TOPBP1, DMC1, SMC4, INCENP. RAD51, OIP5, CDK1, SPC25, CCNB1, BIRC5, NCAPG, ZWINT, MAD2L1, SKA3, NUF2, BUB1B, CENPA, SKA1, AURKB, NEK2, ESCO2, CENPW, HJURP, TTK, NDC80, CDCA5, BUB1, ZWILCH, CENPK, KIF2C, AURKA, DSCC1, CENPN, CDCA8, CENPM, PLK1, MCM6, ERCC6L, CDT1, HELLS, CHEK1, SPAG5, CENPH, PCNA, SPC24, CENPI, NUP37, FEN1, chromosomal 94 0 CENPL, BLM, KIF18A, CENPE, MCM4, BUB3, SUV39H2, MCM2, CDK2, PIF1, DNA2, region CENPO, CENPF, CHEK2, DSN1, H2AFX, MCM7, SUV39H1, MTBP, CBX3, RECQL4, KNTC1, PPP1CC, CENPP, CENPQ, PTGES3, NCAPD2, DYNLL1, SKA2, HAT1, NUP107, MCM5, MCM3, MSH2, BRCA2, NUP85, SSB, ITGB3BP, DMC1, INCENP, THOC3, XPO1, APEX1, XRCC5, KIF22, DCLRE1A, SEH1L, XRCC3, NSMCE2, RAD21. -
UHRF1 Depletion Suppresses Growth of Gallbladder Cancer Cells Through Induction of Apoptosis and Cell Cycle Arrest
ONCOLOGY REPORTS 31: 2635-2643, 2014 UHRF1 depletion suppresses growth of gallbladder cancer cells through induction of apoptosis and cell cycle arrest YIYU QIN1, JIANDONG WANG1, WEI GONG1, MINGDI ZHANG1, ZHAOHUI TANG1, JUN ZHANG2 and ZHIWEI QUAN1 1Department of General Surgery and 2Ministry of Education-Shanghai Key Laboratory of Children's Environmental Health, Xinhua Hospital Affiliated to Shanghai Jiaotong University School of Medicine, Shanghai 200092, P.R. China Received December 28, 2013; Accepted February 21, 2014 DOI: 10.3892/or.2014.3145 Abstract. Ubiquitin-like containing PHD and RING finger proliferation and migration of GBC cells and may serve as a domains 1 (UHRF1), overexpressed in various human biomarker or even a therapeutic target for GBC. malignancies, functions as an important regulator in cell proliferation and epigenetic regulation. Depletion of UHRF1 Introduction has shown potential antitumor activities in several types of cancer. However, the role of UHRF1 in gallbladder cancer Gallbladder cancer (GBC) represents the most frequent and (GBC) has not been investigated. RT-PCR, western blotting aggressive type among biliary tract malignancies. Although and immunohistochemistry were performed to examine recent advances have been made in the diagnosis and treatment, UHRF1 expression at mRNA and protein levels in GBC tissues GBC has a poor overall prognosis with a 5-year survival rate and cell lines. UHRF1 siRNA and UHRF1 shRNA were used <10% (1). Currently, radical resection remains the mainstay of to deplete the expression of UHRF1. The results showed treatment for GBC. However, due to lacking typical symptoms that UHRF1 was overexpressed in GBC and its expression and specific biomarkers, most GBC patients are diagnosed correlated with advanced TNM stage and presence of lymph at advanced stages with unresectable tumors. -
Dissection of the Cellular Function of the ZBED6 Transcription Factor in Mouse
bioRxiv preprint doi: https://doi.org/10.1101/540914; this version posted February 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 1 Dissection of the cellular function of the ZBED6 transcription factor in mouse 2 myoblast cells using gene editing, RNAseq and proteomics 3 4 Shady Younis1, Rakan Naboulsi1, Xuan Wang2, Xiaofang Cao1, Mårten Larsson1, Ernest 5 Sargsyan2, Peter Bergsten2, Nils Welsh2, Leif Andersson1,3,4 6 7 1Science for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala 8 University, SE-751 23 Uppsala, Sweden. 2Science for Life Laboratory, Department of Medical 9 Cell Biology, Uppsala University, SE-751 23 Uppsala, Sweden. 3Department of Animal 10 Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75007 Uppsala, 11 Sweden. 4Department of Veterinary Integrative Biosciences, Texas A&M University, College 12 Station, TX 77843, USA. 13 14 15 1 bioRxiv preprint doi: https://doi.org/10.1101/540914; this version posted February 5, 2019. The copyright holder for this preprint (which was not certified by peer review) is the author/funder. All rights reserved. No reuse allowed without permission. 16 SUMMARY 17 The transcription factor ZBED6 acts as a repressor of Igf2 and affects directly or indirectly the 18 transcriptional regulation of thousands of genes. Here, we use gene editing in mouse C2C12 19 myoblasts and show that ZBED6 regulates Igf2 exclusively through its binding site 5′-GGCTCG- Δ 20 3′ in intron 1 of Igf2. Deletion of this motif (Igf2 GGCT) or complete ablation of Zbed6 leads to 21 ~20-fold up-regulation of IGF2 protein. -
Transcriptional Modulator ZBED6 Affects Cell Cycle and Growth of Human Colorectal Cancer Cells
Transcriptional modulator ZBED6 affects cell cycle and growth of human colorectal cancer cells Muhammad Akhtar Alia,1, Shady Younisb,c,1, Ola Wallermand, Rajesh Guptab, Leif Anderssonb,d,e,1,2, and Tobias Sjöbloma,1 aScience For Life Laboratory, Department of Immunology, Genetics and Pathology, Uppsala University, SE-751 85 Uppsala, Sweden; bScience for Life Laboratory, Department of Medical Biochemistry and Microbiology, Uppsala University, SE-751 85 Uppsala, Sweden; cDepartment of Animal Production, Ain Shams University, Shoubra El-Kheima, 11241 Cairo, Egypt; dDepartment of Animal Breeding and Genetics, Swedish University of Agricultural Sciences, SE-75007 Uppsala, Sweden; and eDepartment of Veterinary Integrative Biosciences, College of Veterinary Medicine and Biomedical Sciences, Texas A&M University, College Station, TX 77843 Contributed by Leif Andersson, May 15, 2015 (sent for review December 10, 2014; reviewed by Jan-Ake Gustafsson) The transcription factor ZBED6 (zinc finger, BED-type containing 6) (QTN) with a large impact on body composition (muscle growth is a repressor of IGF2 whose action impacts development, cell pro- and fat deposition); mutant animals showed threefold higher IGF2 liferation, and growth in placental mammals. In human colorectal expression in postnatal muscle (11). ZBED6 was identified as the cancers, IGF2 overexpression is mutually exclusive with somatic nuclear factor specifically binding the wild-type IGF2 sequence but mutations in PI3K signaling components, providing genetic evi- not the mutated site. ChIP sequencing (ChIP-seq) in mouse C2C12 dence for a role in the PI3K pathway. To understand the role of cells identified more than 1,200 putative ZBED6 target genes, in- ZBED6 in tumorigenesis, we engineered and validated somatic cell cluding 262 genes encoding transcription factors (6). -
Uhrf1-Mediated Tnf-Α Gene Methylation Controls
Uhrf1-Mediated Tnf-α Gene Methylation Controls Proinflammatory Macrophages in Experimental Colitis Resembling Inflammatory Bowel Disease This information is current as of September 30, 2021. Shanshan Qi, Yongkui Li, Zheng Dai, Mengxi Xiang, Guobin Wang, Lin Wang and Zheng Wang J Immunol published online 14 October 2019 http://www.jimmunol.org/content/early/2019/10/12/jimmun ol.1900467 Downloaded from Supplementary http://www.jimmunol.org/content/suppl/2019/10/12/jimmunol.190046 Material 7.DCSupplemental http://www.jimmunol.org/ Why The JI? Submit online. • Rapid Reviews! 30 days* from submission to initial decision • No Triage! Every submission reviewed by practicing scientists • Fast Publication! 4 weeks from acceptance to publication by guest on September 30, 2021 *average Subscription Information about subscribing to The Journal of Immunology is online at: http://jimmunol.org/subscription Permissions Submit copyright permission requests at: http://www.aai.org/About/Publications/JI/copyright.html Email Alerts Receive free email-alerts when new articles cite this article. Sign up at: http://jimmunol.org/alerts The Journal of Immunology is published twice each month by The American Association of Immunologists, Inc., 1451 Rockville Pike, Suite 650, Rockville, MD 20852 Copyright © 2019 by The American Association of Immunologists, Inc. All rights reserved. Print ISSN: 0022-1767 Online ISSN: 1550-6606. Published October 14, 2019, doi:10.4049/jimmunol.1900467 The Journal of Immunology Uhrf1-Mediated Tnf-a Gene Methylation Controls Proinflammatory Macrophages in Experimental Colitis Resembling Inflammatory Bowel Disease Shanshan Qi,*,1 Yongkui Li,*,1 Zheng Dai,* Mengxi Xiang,* Guobin Wang,*,† Lin Wang,*,‡ and Zheng Wang*,† Macrophages drive the pathological process of inflammatory bowel diseases (IBD) mostly by secreting proinflammatory cytokines, such as Tnf-a. -
Genome-Wide DNA Methylation Analysis Reveals Molecular Subtypes of Pancreatic Cancer
www.impactjournals.com/oncotarget/ Oncotarget, 2017, Vol. 8, (No. 17), pp: 28990-29012 Research Paper Genome-wide DNA methylation analysis reveals molecular subtypes of pancreatic cancer Nitish Kumar Mishra1 and Chittibabu Guda1,2,3,4 1Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center, Omaha, NE, 68198, USA 2Bioinformatics and Systems Biology Core, University of Nebraska Medical Center, Omaha, NE, 68198, USA 3Department of Biochemistry and Molecular Biology, University of Nebraska Medical Center, Omaha, NE, 68198, USA 4Fred and Pamela Buffet Cancer Center, University of Nebraska Medical Center, Omaha, NE, 68198, USA Correspondence to: Chittibabu Guda, email: [email protected] Keywords: TCGA, pancreatic cancer, differential methylation, integrative analysis, molecular subtypes Received: October 20, 2016 Accepted: February 12, 2017 Published: March 07, 2017 Copyright: Mishra et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC-BY), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. ABSTRACT Pancreatic cancer (PC) is the fourth leading cause of cancer deaths in the United States with a five-year patient survival rate of only 6%. Early detection and treatment of this disease is hampered due to lack of reliable diagnostic and prognostic markers. Recent studies have shown that dynamic changes in the global DNA methylation and gene expression patterns play key roles in the PC development; hence, provide valuable insights for better understanding the initiation and progression of PC. In the current study, we used DNA methylation, gene expression, copy number, mutational and clinical data from pancreatic patients. -
M Phase Phosphorylation of the Epigenetic Regulator UHRF1 Regulates Its Physical Association with the Deubiquitylase USP7 and Stability
M phase phosphorylation of the epigenetic regulator UHRF1 regulates its physical association with the deubiquitylase USP7 and stability Honghui Maa,1, Hao Chena,1, Xue Guoa,1, Zhentian Wanga, Mathew E. Sowab, Lijuan Zhenga, Shibin Hua, Pingyao Zenga, Rui Guoa, Jianbo Diaoa, Fei Lanc, J. Wade Harperb, Yujiang Geno Shia,d, Yanhui Xua,e,2, and Yang Shia,b,f,g,2 aLaboratory of Epigenetics, Institute of Biomedical Sciences, and Department of Biochemistry, Fudan University Medical School, 138 Yixue Yuan Road, Shanghai 200032, China; bDepartment of Cell Biology, Harvard Medical School, 77 Avenue Louis Pasteur, Boston, MA 02115; cConstellation Pharmaceuticals, 215 First Street, Cambridge, MA 02140; dEndocrinology Division, Brigham and Women Hospital, Harvard Medical School, Boston, MA 02115; eState Key Laboratory of Genetic Engineering, School of Life Sciences, Fudan University, Shanghai 200433, China; fDepartment of Biochemistry, Fudan University Medical School, 138 Yixue Yuan Road, Shanghai 200032, China; and gDivision of Newborn Medicine and Program in Epigenetics, Department of Medicine, Children’s Hospital, Harvard Medical School, 300 Longwood Avenue, Boston, MA 02115 Edited by Tony Hunter, The Salk Institute for Biological Studies, La Jolla, CA, and approved January 27, 2012 (received for review October 7, 2011) UHRF1 (Ubiquitin-like, with PHD and RING finger domains 1) plays question, we have recently undertaken a proteomics approach an important role in DNA CpG methylation, heterochromatin and identified a cell cycle signaling-regulated physical interaction function and gene expression. Overexpression of UHRF1 has been of UHRF1 with the deubiquitylase USP7 (HAUSP) (8, 9) and suggested to contribute to tumorigenesis. However, regulation of demonstrated that it is important for protecting UHRF1 from UHRF1 is largely unknown. -
P90 and UHRF1, Two Novel Regulators of the P53 Signaling Pathway
p90 and UHRF1, Two Novel Regulators of the p53 Signaling Pathway Chao Dai Submitted in partial fulfillment of the Requirements for the degree of Doctor of Philosophy in the Graduate School of Arts and Sciences COLUMBIA UNIVERSITY 2014 ©2013 Chao Dai All Rights Reserved ABSTRACT p90 and UHRF1, Two Novel Regulators of the p53 Signaling Pathway Chao Dai To ensure proper and differentiated regulation of stress response pathways, the p53 tumor suppressor calls for an intricate network of control of activation and fine tuning of transcription activity, which is offered largely through post- translational modifications. Accumulating evidence supports the indispensability of acetylation in the activation of p53 function and indicates modulation of cell fate decision; however the underlying molecular mechanisms are not well understood and identification of the regulatory mechanisms controlling p53 acetylation remains an important step in furthering the understanding of p53 regulation in vivo. In this study we identify p90 and UHRF1 as two novel members of the p53 regulatory network upstream of TIP60-mediated p53 acetylation. Through biochemical purification, p90 was identified as a unique regulator for p53. p90 (also called CCDC8, coiled-coil domain containing 8) interacts with p53 both in vitro and in vivo. Depletion of p90 by RNAi has no obvious effect on p53 stability or p53-mediated activation of p21, but specifically abrogates PUMA activation. Moreover, p90 also interacts with the TIP60 acetyltransferase and stimulates TIP60-dependent Lys120 acetylation of p53, therefore enhancing the apoptotic response of p53. These data reveal p90 as an upstream regulator of the Tip60-p53 interaction and demonstrate that p90 is specifically required for p53- mediated apoptosis upon DNA damage. -
Coordinated Dialogue Between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns
G C A T T A C G G C A T genes Review Coordinated Dialogue between UHRF1 and DNMT1 to Ensure Faithful Inheritance of Methylated DNA Patterns Christian Bronner 1,*, Mahmoud Alhosin 2, Ali Hamiche 1 and Marc Mousli 3 1 Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg, INSERM U1258 CNRS UMR 7104, 1 rue Laurent Fries, 67404, Illkirch, France; [email protected] 2 Department of Biochemistry, Faculty of Science and Cancer and Mutagenesis Unit, King Fahd Medical Research Center, King Abdulaziz University, Jeddah, Saudi Arabia; [email protected] 3 Laboratoire de Bioimagerie et Pathologies, Faculté de Pharmacie, Université de Strasbourg, CNRS UMR 7021, 67401 Illkirch, France; [email protected] * Correspondence: [email protected]; Tel.: +33-88-65-33-48 Received: 26 November 2018; Accepted: 11 January 2019; Published: 18 January 2019 Abstract: DNA methylation, catalyzed by DNA methyltransferases (DNMTs), is an epigenetic mark that needs to be faithfully replicated during mitosis in order to maintain cell phenotype during successive cell divisions. This epigenetic mark is located on the 50-carbon of the cytosine mainly within cytosine–phosphate–guanine (CpG) dinucleotides. DNA methylation is asymmetrically positioned on both DNA strands, temporarily generating a hemi-methylated state after DNA replication. Hemi-methylation is a particular status of DNA that is recognized by ubiquitin-like containing plant homeodomain (PHD) and really interesting new gene (RING) finger domains 1 (UHRF1) through its SET- (Su(var)3-9, Enhancer-of-zeste and Trithorax) and RING-associated (SRA) domain. This interaction is considered to be involved in the recruitment of DNMT1 to chromatin in order to methylate the adequate cytosine on the newly synthetized DNA strand.