Journal Article
. 2014 Apr; 15(6):571-9.
doi: 10.1038/ni.2886.

The epigenetic regulator Uhrf1 facilitates the proliferation and maturation of colonic regulatory T cells

Yuuki Obata 1 Yukihiro Furusawa 2 Takaho A Endo 3 Jafar Sharif 4 Daisuke Takahashi 5 Koji Atarashi 6 Manabu Nakayama 7 Satoshi Onawa 5 Yumiko Fujimura 8 Masumi Takahashi 5 Tomokatsu Ikawa 9 Takeshi Otsubo 10 Yuki I Kawamura 10 Taeko Dohi 10 Shoji Tajima 11 Hiroshi Masumoto 12 Osamu Ohara 3 Kenya Honda 13 Shohei Hori 14 Hiroshi Ohno 15 Haruhiko Koseki 4 Koji Hase 16 
  • PMID: 24777532
  •     49 References
  •     74 citations


Intestinal regulatory T cells (Treg cells) are necessary for the suppression of excessive immune responses to commensal bacteria. However, the molecular machinery that controls the homeostasis of intestinal Treg cells has remained largely unknown. Here we report that colonization of germ-free mice with gut microbiota upregulated expression of the DNA-methylation adaptor Uhrf1 in Treg cells. Mice with T cell-specific deficiency in Uhrf1 (Uhrf1(fl/fl)Cd4-Cre mice) showed defective proliferation and functional maturation of colonic Treg cells. Uhrf1 deficiency resulted in derepression of the gene (Cdkn1a) that encodes the cyclin-dependent kinase inhibitor p21 due to hypomethylation of its promoter region, which resulted in cell-cycle arrest of Treg cells. As a consequence, Uhrf1(fl/fl)Cd4-Cre mice spontaneously developed severe colitis. Thus, Uhrf1-dependent epigenetic silencing of Cdkn1a was required for the maintenance of gut immunological homeostasis. This mechanism enforces symbiotic host-microbe interactions without an inflammatory response.

The impact of the gut microbiota on human health: an integrative view.
Jose C Clemente, Luke K Ursell, Laura Wegener Parfrey, Rob Knight.
Cell, 2012 Mar 20; 148(6). PMID: 22424233    Free PMC article.
Highly Cited. Review.
GPR15-mediated homing controls immune homeostasis in the large intestine mucosa.
Sangwon V Kim, Wenkai V Xiang, +7 authors, Dan R Littman.
Science, 2013 May 11; 340(6139). PMID: 23661644    Free PMC article.
Highly Cited.
CDK inhibitors: positive and negative regulators of G1-phase progression.
C J Sherr, J M Roberts.
Genes Dev, 1999 Jul 01; 13(12). PMID: 10385618
Highly Cited. Review.
Uhrf1-dependent H3K23 ubiquitylation couples maintenance DNA methylation and replication.
Atsuya Nishiyama, Luna Yamaguchi, +9 authors, Makoto Nakanishi.
Nature, 2013 Sep 10; 502(7470). PMID: 24013172
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.
Neuropilin 1 is expressed on thymus-derived natural regulatory T cells, but not mucosa-generated induced Foxp3+ T reg cells.
Jonathan M Weiss, Angelina M Bilate, +17 authors, Juan J Lafaille.
J Exp Med, 2012 Sep 12; 209(10). PMID: 22966001    Free PMC article.
Highly Cited.
Microbial influences in inflammatory bowel diseases.
R Balfour Sartor.
Gastroenterology, 2008 Feb 05; 134(2). PMID: 18242222
Highly Cited. Review.
Isolation and subsequent analysis of murine lamina propria mononuclear cells from colonic tissue.
Benno Weigmann, Ingrid Tubbe, +3 authors, Markus F Neurath.
Nat Protoc, 2007 Oct 20; 2(10). PMID: 17947970
Highly Cited.
Genome-wide analysis of DNA methylation and expression of microRNAs in breast cancer cells.
Sumiyo Morita, Ryou-U Takahashi, +9 authors, Izuho Hatada.
Int J Mol Sci, 2012 Sep 04; 13(7). PMID: 22942701    Free PMC article.
Neuropilin-1 distinguishes natural and inducible regulatory T cells among regulatory T cell subsets in vivo.
Mahesh Yadav, Cedric Louvet, +11 authors, Jeffrey A Bluestone.
J Exp Med, 2012 Sep 12; 209(10). PMID: 22966003    Free PMC article.
Highly Cited.
Host-microbe interactions have shaped the genetic architecture of inflammatory bowel disease.
Luke Jostins, Stephan Ripke, +104 authors, Judy H Cho.
Nature, 2012 Nov 07; 491(7422). PMID: 23128233    Free PMC article.
Highly Cited.
Resident enteric bacteria are necessary for development of spontaneous colitis and immune system activation in interleukin-10-deficient mice.
R K Sellon, S Tonkonogy, +5 authors, R B Sartor.
Infect Immun, 1998 Oct 24; 66(11). PMID: 9784526    Free PMC article.
Highly Cited.
Dendritic cell expression of the signaling molecule TRAF6 is critical for gut microbiota-dependent immune tolerance.
Daehee Han, Matthew C Walsh, +14 authors, Yongwon Choi.
Immunity, 2013 Jun 25; 38(6). PMID: 23791643    Free PMC article.
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.
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.
Control of immune responses by antigen-specific regulatory T cells expressing the folate receptor.
Tomoyuki Yamaguchi, Keiji Hirota, +4 authors, Shimon Sakaguchi.
Immunity, 2007 Jul 07; 27(1). PMID: 17613255
Highly Cited.
Intestinal bacterial colonization induces mutualistic regulatory T cell responses.
Markus B Geuking, Julia Cahenzli, +5 authors, Andrew J Macpherson.
Immunity, 2011 May 21; 34(5). PMID: 21596591
Highly Cited.
Phenotypically distinct subsets of CD4+ T cells induce or protect from chronic intestinal inflammation in C. B-17 scid mice.
F Powrie, M W Leach, +2 authors, R L Coffman.
Int Immunol, 1993 Nov 01; 5(11). PMID: 7903159
Highly Cited.
Role of Smad proteins and transcription factor Sp1 in p21(Waf1/Cip1) regulation by transforming growth factor-beta.
K Pardali, A Kurisaki, +3 authors, A Moustakas.
J Biol Chem, 2000 Jul 06; 275(38). PMID: 10878024
The gut microbiota in IBD.
Chaysavanh Manichanh, Natalia Borruel, Francesc Casellas, Francisco Guarner.
Nat Rev Gastroenterol Hepatol, 2012 Aug 22; 9(10). PMID: 22907164
Highly Cited. Review.
The microbial metabolites, short-chain fatty acids, regulate colonic Treg cell homeostasis.
Patrick M Smith, Michael R Howitt, +5 authors, Wendy S Garrett.
Science, 2013 Jul 06; 341(6145). PMID: 23828891    Free PMC article.
Highly Cited.
Metabolites produced by commensal bacteria promote peripheral regulatory T-cell generation.
Nicholas Arpaia, Clarissa Campbell, +8 authors, Alexander Y Rudensky.
Nature, 2013 Nov 15; 504(7480). PMID: 24226773    Free PMC article.
Highly Cited.
Role of conserved non-coding DNA elements in the Foxp3 gene in regulatory T-cell fate.
Ye Zheng, Steven Josefowicz, +3 authors, Alexander Y Rudensky.
Nature, 2010 Jan 15; 463(7282). PMID: 20072126    Free PMC article.
Highly Cited.
Induction and prevention of colonic inflammation in IL-2-deficient mice.
R O Ehrhardt, B R Lúdvíksson, +2 authors, W Strober.
J Immunol, 1997 Jan 15; 158(2). PMID: 8992969
Characterization of clostridia isolated from faeces of limited flora mice and their effect on caecal size when associated with germ-free mice.
K Itoh, T Mitsuoka.
Lab Anim, 1985 Apr 01; 19(2). PMID: 3889493
Treg induction by a rationally selected mixture of Clostridia strains from the human microbiota.
Koji Atarashi, Takeshi Tanoue, +19 authors, Kenya Honda.
Nature, 2013 Jul 12; 500(7461). PMID: 23842501
Highly Cited.
Deregulated T cell activation and autoimmunity in mice lacking interleukin-2 receptor beta.
H Suzuki, T M Kündig, +7 authors, H Griesser.
Science, 1995 Jun 09; 268(5216). PMID: 7770771
Highly Cited.
T cell receptor stimulation-induced epigenetic changes and Foxp3 expression are independent and complementary events required for Treg cell development.
Naganari Ohkura, Masahide Hamaguchi, +12 authors, Shimon Sakaguchi.
Immunity, 2012 Nov 06; 37(5). PMID: 23123060
Highly Cited.
Interleukin-2 receptor alpha chain regulates the size and content of the peripheral lymphoid compartment.
D M Willerford, J Chen, +3 authors, F W Alt.
Immunity, 1995 Oct 01; 3(4). PMID: 7584142
Highly Cited.
Epithelial cell-intrinsic Notch signaling plays an essential role in the maintenance of gut immune homeostasis.
Yuuki Obata, Daisuke Takahashi, +8 authors, Hiroshi Ohno.
J Immunol, 2012 Jan 27; 188(5). PMID: 22279105
Mice lacking p21CIP1/WAF1 undergo normal development, but are defective in G1 checkpoint control.
C Deng, P Zhang, +2 authors, P Leder.
Cell, 1995 Aug 25; 82(4). PMID: 7664346
Highly Cited.
Inducible Foxp3+ regulatory T-cell development by a commensal bacterium of the intestinal microbiota.
June L Round, Sarkis K Mazmanian.
Proc Natl Acad Sci U S A, 2010 Jun 23; 107(27). PMID: 20566854    Free PMC article.
Highly Cited.
Host-derived nitrate boosts growth of E. coli in the inflamed gut.
Sebastian E Winter, Maria G Winter, +13 authors, Andreas J Bäumler.
Science, 2013 Feb 09; 339(6120). PMID: 23393266    Free PMC article.
Highly Cited.
The Toll-like receptor 2 pathway establishes colonization by a commensal of the human microbiota.
June L Round, S Melanie Lee, +4 authors, Sarkis K Mazmanian.
Science, 2011 Apr 23; 332(6032). PMID: 21512004    Free PMC article.
Highly Cited.
Induction of colonic regulatory T cells by indigenous Clostridium species.
Koji Atarashi, Takeshi Tanoue, +14 authors, Kenya Honda.
Science, 2011 Jan 06; 331(6015). PMID: 21205640    Free PMC article.
Highly Cited.
Plasticity of Foxp3(+) T cells reflects promiscuous Foxp3 expression in conventional T cells but not reprogramming of regulatory T cells.
Takahisa Miyao, Stefan Floess, +5 authors, Shohei Hori.
Immunity, 2012 Feb 14; 36(2). PMID: 22326580
Highly Cited.
In vivo expansion of T reg cells with IL-2-mAb complexes: induction of resistance to EAE and long-term acceptance of islet allografts without immunosuppression.
Kylie E Webster, Stacey Walters, +5 authors, Jonathan Sprent.
J Exp Med, 2009 Apr 01; 206(4). PMID: 19332874    Free PMC article.
Highly Cited.
An operational definition of epigenetics.
Shelley L Berger, Tony Kouzarides, Ramin Shiekhattar, Ali Shilatifard.
Genes Dev, 2009 Apr 03; 23(7). PMID: 19339683    Free PMC article.
Highly Cited.
T regulatory cells maintain intestinal homeostasis by suppressing γδ T cells.
Sung-Gyoo Park, Ramkumar Mathur, +4 authors, Sankar Ghosh.
Immunity, 2010 Nov 16; 33(5). PMID: 21074460    Free PMC article.
Inducible IL-2 production by dendritic cells revealed by global gene expression analysis.
F Granucci, C Vizzardelli, +6 authors, P Ricciardi-Castagnoli.
Nat Immunol, 2001 Aug 30; 2(9). PMID: 11526406
Highly Cited.
Methylation in the p21WAF1/cip1 promoter of Apc+/-, p21+/- mice and lack of response to sulindac.
WanCai Yang, Laura Bancroft, Leonard H Augenlicht.
Oncogene, 2005 Feb 03; 24(12). PMID: 15688007
CD25+ CD4+ T cells compete with naive CD4+ T cells for IL-2 and exploit it for the induction of IL-10 production.
Thomas Barthlott, Halima Moncrieffe, +4 authors, Brigitta Stockinger.
Int Immunol, 2005 Feb 03; 17(3). PMID: 15684039
A function for interleukin 2 in Foxp3-expressing regulatory T cells.
Jason D Fontenot, Jeffrey P Rasmussen, Marc A Gavin, Alexander Y Rudensky.
Nat Immunol, 2005 Oct 18; 6(11). PMID: 16227984
Highly Cited.
The gut microbiota shapes intestinal immune responses during health and disease.
June L Round, Sarkis K Mazmanian.
Nat Rev Immunol, 2009 Apr 04; 9(5). PMID: 19343057    Free PMC article.
Highly Cited. Review.
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.
Ulcerative colitis-like disease in mice with a disrupted interleukin-2 gene.
B Sadlack, H Merz, +3 authors, I Horak.
Cell, 1993 Oct 22; 75(2). PMID: 8402910
Highly Cited.
Activation of Gpr109a, receptor for niacin and the commensal metabolite butyrate, suppresses colonic inflammation and carcinogenesis.
Nagendra Singh, Ashish Gurav, +10 authors, Vadivel Ganapathy.
Immunity, 2014 Jan 15; 40(1). PMID: 24412617    Free PMC article.
Highly Cited.
Links between tumor suppressors: p53 is required for TGF-beta gene responses by cooperating with Smads.
Michelangelo Cordenonsi, Sirio Dupont, +3 authors, Stefano Piccolo.
Cell, 2003 May 07; 113(3). PMID: 12732139
Highly Cited.
Commensal microbe-derived butyrate induces the differentiation of colonic regulatory T cells.
Yukihiro Furusawa, Yuuki Obata, +27 authors, Hiroshi Ohno.
Nature, 2013 Nov 15; 504(7480). PMID: 24226770
Highly Cited.
Uhrf to Treg cells: reinforcing the mucosal peacekeepers.
Daniel H D Gray, Adrian Liston.
Nat Immunol, 2014 May 21; 15(6). PMID: 24840991
T cells and intestinal commensal bacteria--ignorance, rejection, and acceptance.
Jiani N Chai, You W Zhou, Chyi-Song Hsieh.
FEBS Lett, 2014 Jul 06; 588(22). PMID: 24997344    Free PMC article.
Metabolic control of regulatory T cell development and function.
Hu Zeng, Hongbo Chi.
Trends Immunol, 2014 Sep 25; 36(1). PMID: 25248463    Free PMC article.
Highly Cited. Review.
Regulatory T cell DNA methyltransferase inhibition accelerates resolution of lung inflammation.
Benjamin D Singer, Jason R Mock, +10 authors, Franco R D'Alessio.
Am J Respir Cell Mol Biol, 2014 Oct 09; 52(5). PMID: 25295995    Free PMC article.
Commensal microbiota regulates T cell fate decision in the gut.
Yukihiro Furusawa, Yuuki Obata, Koji Hase.
Semin Immunopathol, 2014 Oct 16; 37(1). PMID: 25315350
Epigenomics and the microbiota.
Theresa Alenghat.
Toxicol Pathol, 2014 Oct 22; 43(1). PMID: 25330924    Free PMC article.
Epigenomic regulation of host-microbiota interactions.
Theresa Alenghat, David Artis.
Trends Immunol, 2014 Dec 03; 35(11). PMID: 25443494    Free PMC article.
DNA hypomethylation induces a DNA replication-associated cell cycle arrest to block hepatic outgrowth in uhrf1 mutant zebrafish embryos.
Vinitha Jacob, Yelena Chernyavskaya, +4 authors, Kirsten C Sadler.
Development, 2015 Jan 08; 142(3). PMID: 25564650    Free PMC article.
Microbiota-mediated inflammation and antimicrobial defense in the intestine.
Silvia Caballero, Eric G Pamer.
Annu Rev Immunol, 2015 Jan 13; 33. PMID: 25581310    Free PMC article.
Highly Cited. Review.
Epigenetic modifications of the immune system in health and disease.
Yuuki Obata, Yukihiro Furusawa, Koji Hase.
Immunol Cell Biol, 2015 Feb 11; 93(3). PMID: 25666097
Epigenetic control of intestinal barrier function and inflammation in zebrafish.
Lindsay Marjoram, Ashley Alvers, +11 authors, Michel Bagnat.
Proc Natl Acad Sci U S A, 2015 Mar 03; 112(9). PMID: 25730872    Free PMC article.
Intestinal microbiota as modulators of the immune system and neuroimmune system: impact on the host health and homeostasis.
Carlos Magno da Costa Maranduba, Sandra Bertelli Ribeiro De Castro, +9 authors, Fernando de Sá Silva.
J Immunol Res, 2015 Mar 12; 2015. PMID: 25759850    Free PMC article.
Autoimmune host-microbiota interactions at barrier sites and beyond.
William E Ruff, Martin A Kriegel.
Trends Mol Med, 2015 Mar 17; 21(4). PMID: 25771098    Free PMC article.
IBD. Fishing for missing heritability in IBD.
Michael Pack.
Nat Rev Gastroenterol Hepatol, 2015 May 06; 12(6). PMID: 25942704
Influence of nutrient-derived metabolites on lymphocyte immunity.
Marc Veldhoen, Cristina Ferreira.
Nat Med, 2015 Jun 30; 21(7). PMID: 26121194
Genetically engineered mouse models for studying inflammatory bowel disease.
Atsushi Mizoguchi, Takahito Takeuchi, +2 authors, Emiko Mizoguchi.
J Pathol, 2015 Sep 22; 238(2). PMID: 26387641    Free PMC article.
Metagenomic cross-talk: the regulatory interplay between immunogenomics and the microbiome.
Maayan Levy, Christoph A Thaiss, Eran Elinav.
Genome Med, 2015 Nov 22; 7. PMID: 26589591    Free PMC article.
CD4+ T-cell subsets in inflammatory diseases: beyond the Th1/Th2 paradigm.
Kiyoshi Hirahara, Toshinori Nakayama.
Int Immunol, 2016 Feb 14; 28(4). PMID: 26874355    Free PMC article.
Highly Cited. Review.
Comprehensive and computational analysis of genes in human umbilical vein endothelial cells responsive to X-irradiation.
Yukihiro Furusawa, Qing-Li Zhao, +4 authors, Takashi Kondo.
Genom Data, 2016 Jun 09; 8. PMID: 27275413    Free PMC article.
Contribution of Mesenteric Lymph Nodes and GALT to the Intestinal Foxp3+ Regulatory T-Cell Compartment.
Duke Geem, Vu Ngo, +4 authors, Timothy L Denning.
Cell Mol Gastroenterol Hepatol, 2016 Aug 30; 2(3). PMID: 27570813    Free PMC article.
Epigenetic Variability of CD4+CD25+ Tregs Contributes to the Pathogenesis of Autoimmune Diseases.
Ye Shu, Qinghua Hu, +3 authors, Rong Xiao.
Clin Rev Allergy Immunol, 2016 Oct 01; 52(2). PMID: 27687891
Roles for Intestinal Bacteria, Viruses, and Fungi in Pathogenesis of Inflammatory Bowel Diseases and Therapeutic Approaches.
R Balfour Sartor, Gary D Wu.
Gastroenterology, 2016 Oct 23; 152(2). PMID: 27769810    Free PMC article.
Highly Cited. Review.
Loss of Uhrf1 in neural stem cells leads to activation of retroviral elements and delayed neurodegeneration.
Vidya Ramesh, Efil Bayam, +5 authors, Magdalena Götz.
Genes Dev, 2016 Nov 01; 30(19). PMID: 27798843    Free PMC article.
RelA NF-κB subunit activation as a therapeutic target in diffuse large B-cell lymphoma.
Mingzhi Zhang, Zijun Y Xu-Monette, +24 authors, Ken H Young.
Aging (Albany NY), 2016 Dec 13; 8(12). PMID: 27941215    Free PMC article.
Uhrf1 controls the self-renewal versus differentiation of hematopoietic stem cells by epigenetically regulating the cell-division modes.
Jingyao Zhao, Xufeng Chen, +3 authors, Xiaolong Liu.
Proc Natl Acad Sci U S A, 2016 Dec 14; 114(2). PMID: 27956603    Free PMC article.
Host-microbiota interactions: epigenomic regulation.
Vivienne Woo, Theresa Alenghat.
Curr Opin Immunol, 2017 Jan 20; 44. PMID: 28103497    Free PMC article.
Influences of the Gut Microbiota on DNA Methylation and Histone Modification.
Jianzhong Ye, Wenrui Wu, Yating Li, Lanjuan Li.
Dig Dis Sci, 2017 Mar 28; 62(5). PMID: 28341870
Induction of Colonic Regulatory T Cells by Mesalamine by Activating the Aryl Hydrocarbon Receptor.
Kyoko Oh-Oka, Yuko Kojima, +9 authors, Atsuhito Nakao.
Cell Mol Gastroenterol Hepatol, 2017 Jun 09; 4(1). PMID: 28593185    Free PMC article.
UHRF1 is required for basal stem cell proliferation in response to airway injury.
Handan Xiang, Lifeng Yuan, +13 authors, Xiao-Fan Wang.
Cell Discov, 2017 Jun 20; 3. PMID: 28626588    Free PMC article.
Immunological effects of hypomethylating agents.
Katherine E Lindblad, Meghali Goswami, Christopher S Hourigan, Karolyn A Oetjen.
Expert Rev Hematol, 2017 Jun 24; 10(8). PMID: 28644756    Free PMC article.
CDK4/6 inhibition triggers anti-tumour immunity.
Shom Goel, Molly J DeCristo, +17 authors, Jean J Zhao.
Nature, 2017 Aug 17; 548(7668). PMID: 28813415    Free PMC article.
Highly Cited.
decodeRNA- predicting non-coding RNA functions using guilt-by-association.
Steve Lefever, Jasper Anckaert, +3 authors, Pieter Mestdagh.
Database (Oxford), 2017 Dec 09; 2017. PMID: 29220434    Free PMC article.
High self-reactivity drives T-bet and potentiates Treg function in tissue-specific autoimmunity.
Maran L Sprouse, Marissa A Scavuzzo, +6 authors, Maria Bettini.
JCI Insight, 2018 Jan 26; 3(2). PMID: 29367462    Free PMC article.
UHRF1 epigenetically orchestrates smooth muscle cell plasticity in arterial disease.
Leonardo Elia, Paolo Kunderfranco, +8 authors, Manuela Quintavalle.
J Clin Invest, 2018 Mar 21; 128(6). PMID: 29558369    Free PMC article.
Uhrf1 regulates germinal center B cell expansion and affinity maturation to control viral infection.
Chao Chen, Sulan Zhai, +6 authors, Xiaoming Wang.
J Exp Med, 2018 Apr 06; 215(5). PMID: 29618490    Free PMC article.
DNA methylation regulates the neonatal CD4+ T-cell response to pneumonia in mice.
Sharon A McGrath-Morrow, Roland Ndeh, +6 authors, Benjamin D Singer.
J Biol Chem, 2018 Jun 06; 293(30). PMID: 29866884    Free PMC article.
Long noncoding RNA UPAT promoted cell proliferation via increasing UHRF1 expression in non-small cell lung cancer.
Haiqin Wang, Dakui Cao, Fengjie Wu.
Oncol Lett, 2018 Jul 17; 16(2). PMID: 30008828    Free PMC article.
Roles of intestinal microbiota in response to cancer immunotherapy.
Jing Cong, Xiaochun Zhang.
Eur J Clin Microbiol Infect Dis, 2018 Sep 14; 37(12). PMID: 30209679
Identifying deer antler uhrf1 proliferation and s100a10 mineralization genes using comparative RNA-seq.
Dai Fei Elmer Ker, Dan Wang, +7 authors, Yunzhi Peter Yang.
Stem Cell Res Ther, 2018 Nov 01; 9(1). PMID: 30376879    Free PMC article.
TGF-β signaling controls Foxp3 methylation and T reg cell differentiation by modulating Uhrf1 activity.
Xiang Sun, Yu Cui, +2 authors, Xiaolong Liu.
J Exp Med, 2019 Sep 14; 216(12). PMID: 31515281    Free PMC article.
Mucin O-glycans facilitate symbiosynthesis to maintain gut immune homeostasis.
Takahiro Yamada, Shingo Hino, +15 authors, Koji Hase.
EBioMedicine, 2019 Sep 16; 48. PMID: 31521614    Free PMC article.
Transgenerational epigenetic inheritance: from phenomena to molecular mechanisms.
Noa Liberman, Simon Yuan Wang, Eric Lieberman Greer.
Curr Opin Neurobiol, 2019 Oct 22; 59. PMID: 31634674    Free PMC article.
Demystifying the manipulation of host immunity, metabolism, and extraintestinal tumors by the gut microbiome.
Ziying Zhang, Haosheng Tang, +2 authors, Yongguang Tao.
Signal Transduct Target Ther, 2019 Oct 23; 4. PMID: 31637019    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.
Determinants of IBD Heritability: Genes, Bugs, and More.
Williams Turpin, Ashleigh Goethel, Larbi Bedrani, Kenneth Croitoru Mdcm.
Inflamm Bowel Dis, 2018 Apr 28; 24(6). PMID: 29701818    Free PMC article.
Requirement for POH1 in differentiation and maintenance of regulatory T cells.
Yun Liu, Li Zhang, +8 authors, Yongzhong Liu.
Cell Death Differ, 2018 Jul 25; 26(4). PMID: 30038387    Free PMC article.
Epigenetic regulator UHRF1 inactivates REST and growth suppressor gene expression via DNA methylation to promote axon regeneration.
Young Mi Oh, Marcus Mahar, +3 authors, Valeria Cavalli.
Proc Natl Acad Sci U S A, 2018 Dec 12; 115(52). PMID: 30530687    Free PMC article.
Genome-wide CRISPR Screens in T Helper Cells Reveal Pervasive Crosstalk between Activation and Differentiation.
Johan Henriksson, Xi Chen, +8 authors, Sarah A Teichmann.
Cell, 2019 Jan 15; 176(4). PMID: 30639098    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.
Transcriptional analysis of Foxp3+ Tregs and functions of two identified molecules during resolution of ALI.
Jason R Mock, Catherine F Dial, +6 authors, Claire M Doerschuk.
JCI Insight, 2019 Feb 13; 4(6). PMID: 30753170    Free PMC article.
UHRF genes regulate programmed interdigital tissue regression and chondrogenesis in the embryonic limb.
Cristina Sanchez-Fernandez, Carlos I Lorda-Diez, +2 authors, Juan M Hurlé.
Cell Death Dis, 2019 Apr 27; 10(5). PMID: 31024001    Free PMC article.
Epigenetic and inflammatory events in experimental periodontitis following systemic microbial challenge.
Daniela B Palioto, Livia S Finoti, Denis F Kinane, Manjunatha Benakanakere.
J Clin Periodontol, 2019 May 28; 46(8). PMID: 31131910    Free PMC article.
Epigenetic Compensation Promotes Liver Regeneration.
Shuang Wang, Chi Zhang, +7 authors, Kirsten C Sadler.
Dev Cell, 2019 Jun 25; 50(1). PMID: 31231040    Free PMC article.
Transcriptional Regulation of Differentiation and Functions of Effector T Regulatory Cells.
Shin-Ichi Koizumi, Hiroki Ishikawa.
Cells, 2019 Aug 23; 8(8). PMID: 31434282    Free PMC article.
Combined IL-2 Immunocomplex and Anti-IL-5 mAb Treatment Expands Foxp3+ Treg Cells in the Absence of Eosinophilia and Ameliorates Experimental Colitis.
Hirohito Abo, Kyle L Flannigan, +3 authors, Timothy L Denning.
Front Immunol, 2019 Apr 02; 10. PMID: 30930900    Free PMC article.
Epithelial Cells as a Transmitter of Signals From Commensal Bacteria and Host Immune Cells.
Yoshiyuki Goto.
Front Immunol, 2019 Sep 27; 10. PMID: 31555282    Free PMC article.
CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes.
Chikako Shimokawa, Tamotsu Kato, +12 authors, Hajime Hisaeda.
Nat Commun, 2020 Apr 24; 11(1). PMID: 32321922    Free PMC article.
UHRF1: a jack of all trades, and a master epigenetic regulator during spermatogenesis.
Simon J Newkirk, Wenfeng An.
Biol Reprod, 2020 Feb 27; 102(6). PMID: 32101289    Free PMC article.
Role of RING-Type E3 Ubiquitin Ligases in Inflammatory Signalling and Inflammatory Bowel Disease.
Liguo Zhu, Ying Li, +5 authors, Shenghong Zhang.
Mediators Inflamm, 2020 Aug 28; 2020. PMID: 32848509    Free PMC article.
Epigenetic mechanism and target therapy of UHRF1 protein complex in malignancies.
Busheng Xue, Jiansong Zhao, +3 authors, Yan Li.
Onco Targets Ther, 2019 Jan 23; 12. PMID: 30666134    Free PMC article.
BjussuLAAO-II induces cytotoxicity and alters DNA methylation of cell-cycle genes in monocultured/co-cultured HepG2 cells.
Ana Rita Thomazela Machado, Alexandre Ferro Aissa, +3 authors, Lusânia Maria Greggi Antunes.
J Venom Anim Toxins Incl Trop Dis, 2019 May 28; 25. PMID: 31131003    Free PMC article.
Immunomodulation by anticancer cell cycle inhibitors.
Giulia Petroni, Silvia C Formenti, Selina Chen-Kiang, Lorenzo Galluzzi.
Nat Rev Immunol, 2020 Apr 30; 20(11). PMID: 32346095    Free PMC article.
Bone Morphogenic Proteins Are Immunoregulatory Cytokines Controlling FOXP3+ Treg Cells.
Lauren M Browning, Caroline Miller, +6 authors, Piotr Kraj.
Cell Rep, 2020 Oct 08; 33(1). PMID: 33027660    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.
UHRF1 downregulation promotes T follicular helper cell differentiation by increasing BCL6 expression in SLE.
Limin Liu, Longyuan Hu, +8 authors, Ming Zhao.
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Single-nucleotide methylation specifically represses type I interferon in antiviral innate immunity.
Zheng-Jun Gao, Wen-Ping Li, +8 authors, Yi-Yuan Li.
J Exp Med, 2021 Feb 23; 218(3). PMID: 33616624    Free PMC article.
uhrf1 and dnmt1 Loss Induces an Immune Response in Zebrafish Livers Due to Viral Mimicry by Transposable Elements.
Elena Magnani, Filippo Macchi, +3 authors, Kirsten C Sadler.
Front Immunol, 2021 Apr 16; 12. PMID: 33854502    Free PMC article.
Epigenome-metabolome-microbiome axis in health and IBD.
Hajera Amatullah, Kate L Jeffrey.
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PIP4Ks impact on PI3K, FOXP3, and UHRF1 signaling and modulate human regulatory T cell proliferation and immunosuppressive activity.
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Metabolic Controls on Epigenetic Reprogramming in Regulatory T Cells.
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Front Immunol, 2021 Aug 24; 12. PMID: 34421930    Free PMC article.
Epigenetic regulation by gut microbiota.
Vivienne Woo, Theresa Alenghat.
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Transcriptional changes in dendritic cells underlying allergen specific induced tolerance in a mouse model.
Rafael Nuñez, Maria Jose Rodriguez, +9 authors, Cristobalina Mayorga.
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Uhrf1 governs the proliferation and differentiation of muscle satellite cells.
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