Structural and mechanistic insights into UHRF1-mediated DNMT1 activation in the maintenance DNA methylation

Nucleic Acids Research
Tao LiChengmin Qian

Abstract

UHRF1 plays multiple roles in regulating DNMT1-mediated DNA methylation maintenance during DNA replication. The UHRF1 C-terminal RING finger functions as an ubiquitin E3 ligase to establish histone H3 ubiquitination at Lys18 and/or Lys23, which is subsequently recognized by DNMT1 to promote its localization onto replication foci. Here, we present the crystal structure of DNMT1 RFTS domain in complex with ubiquitin and highlight a unique ubiquitin binding mode for the RFTS domain. We provide evidence that UHRF1 N-terminal ubiquitin-like domain (UBL) also binds directly to DNMT1. Despite sharing a high degree of structural similarity, UHRF1 UBL and ubiquitin bind to DNMT1 in a very distinct fashion and exert different impacts on DNMT1 enzymatic activity. We further show that the UHRF1 UBL-mediated interaction between UHRF1 and DNMT1, and the binding of DNMT1 to ubiquitinated histone H3 that is catalyzed by UHRF1 RING domain are critical for the proper subnuclear localization of DNMT1 and maintenance of DNA methylation. Collectively, our study adds another layer of complexity to the regulatory mechanism of DNMT1 activation by UHRF1 and supports that individual domains of UHRF1 participate and act in concert to maintain DNA methyla...Continue Reading

References

Nov 1, 1995·Journal of Biomolecular NMR·F DelaglioA Bax
Dec 2, 2004·Acta Crystallographica. Section D, Biological Crystallography·Paul Emsley, Kevin Cowtan
Jul 12, 2005·Nature Structural & Molecular Biology·Shahri RaasiCecile M Pickart
Mar 7, 2007·Nature Reviews. Genetics·Manel Esteller
Aug 4, 2007·Science·Magnolia BostickSteven E Jacobsen
Apr 1, 2008·Molecular Cell·Vikki M Weake, Jerry L Workman
Aug 13, 2008·Protein Expression and Purification·Kokoro Hayashi, Chojiro Kojima
Sep 6, 2008·Nature·Hideharu HashimotoXiaodong Cheng
Oct 24, 2008·The Journal of Biological Chemistry·Chengmin QianMing-Ming Zhou
Sep 24, 2009·Nature Reviews. Molecular Cell Biology·Ivan DikicKylie J Walters
Jan 13, 2010·Molecular Cell·Daoning ZhangDavid Fushman
Feb 4, 2010·Acta Crystallographica. Section D, Biological Crystallography·Paul D AdamsPeter H Zwart
Jun 15, 2010·Molecular Cell·Jason M Winget, Thibault Mayor
Mar 11, 2011·The Journal of Biological Chemistry·Farisa SyedaCharles Brenner
Apr 27, 2011·Proceedings of the National Academy of Sciences of the United States of America·Kohei TakeshitaShoji Tajima
May 3, 2011·Nature Genetics·Christopher J KleinPeter J Dyck
Apr 25, 2012·Annual Review of Biochemistry·David Komander, Michael Rape
May 29, 2012·Chemistry & Biology·Pavel BashtrykovAlbert Jeltsch
Jul 28, 2012·Proceedings of the National Academy of Sciences of the United States of America·Kyohei AritaMasahiro Shirakawa
Sep 18, 2012·Cell·Francesca MattiroliTitia K Sixma
Oct 30, 2012·Molecular Cell·Kelly M Trujillo, Mary Ann Osley
Feb 13, 2013·Nature Reviews. Genetics·Zachary D Smith, Alexander Meissner
Feb 19, 2013·Molecular Cell·Stephen P Jackson, Daniel Durocher
Feb 20, 2015·Nature Reviews. Cancer·Liubin YangMargaret A Goodell
Jun 14, 2015·Journal of Molecular Biology·Zhi-Min ZhangJikui Song
Jan 1, 1997·Methods in Enzymology·Zbyszek Otwinowski, Wladek Minor
Mar 24, 2017·Human Molecular Genetics·Martha SmetsHeinrich Leonhardt

❮ Previous
Next ❯

Citations

Oct 21, 2018·The Journal of Biological Chemistry·Olya YarychkivskaTimothy H Bestor
Oct 26, 2018·Bioscience Reports·Haixia ZhangXianzheng Wu
Jul 20, 2019·Chemistry : a European Journal·Liliyana ZaayterYves Mély
Jul 17, 2019·Journal of Peptide Science : an Official Publication of the European Peptide Society·Toru KawakamiIsao Suetake
Nov 5, 2019·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·Yuichi MishimaIsao Suetake
Oct 20, 2018·PLoS Genetics·Anna MotnenkoMartin A Cohn
May 3, 2020·The Journal of Immunology : Official Journal of the American Association of Immunologists·Yiwen ZhangHui Zhang
Dec 10, 2019·Annual Review of Biochemistry·Zhiyuan Chen, Yi Zhang
May 30, 2020·Integrative and Comparative Biology·C BiwerF Silvestre
Aug 15, 2018·Proceedings of the National Academy of Sciences of the United States of America·Robert M VaughanScott B Rothbart
Aug 28, 2020·Mediators of Inflammation·Liguo ZhuShenghong Zhang
Aug 30, 2018·Biochemical Society Transactions·Humaira Gowher, Albert Jeltsch
Jul 18, 2020·Proceedings of the National Academy of Sciences of the United States of America·Wendan RenJikui Song
Nov 12, 2020·Experimental Biology and Medicine·Xi HeJingshan Shi
Dec 11, 2020·Nucleic Acids Research·Nataliya PetrykPierre-Antoine Defossez
Apr 14, 2020·Computational and Structural Biotechnology Journal·Zhongjie LiangGuang Hu
Oct 19, 2019·Pharmacology & Therapeutics·Parinaz MehdipourDaniel D De Carvalho
Nov 19, 2020·Chromosome Research : an International Journal on the Molecular, Supramolecular and Evolutionary Aspects of Chromosome Biology·Musashi Kubiura-IchimaruMasako Tada
Jan 25, 2021·Trends in Genetics : TIG·Francesca Mattiroli, Lorenza Penengo
Nov 20, 2020·Molecular Therapy : the Journal of the American Society of Gene Therapy·Xueying GengYanzhi Du
Mar 7, 2021·International Journal of Molecular Sciences·Hongni XueZekun Guo
Mar 28, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xuan MingYingfeng Li
Apr 3, 2021·Seminars in Cancer Biology·Wesley N Saintilnord, Yvonne Fondufe-Mittendorf
Jun 15, 2021·Trends in Genetics : TIG·Atsuya Nishiyama, Makoto Nakanishi
Aug 8, 2021·Journal of Genetics and Genomics = Yi Chuan Xue Bao·Xuezhu WangYang Chen
Nov 8, 2021·The Science of the Total Environment·Gerhard P AignerMartina Höckner

❮ Previous
Next ❯

Methods Mentioned

BETA
nuclear
isothermal titration calorimetry
size-exclusion chromatography
confocal microscopy
NMR
chemical shift
electrophoresis
ubiquitination

Software Mentioned

Phenix
NMRPipe
COOT
NMRView

Related Concepts

Trending Feeds

COVID-19

Coronaviruses encompass a large family of viruses that cause the common cold as well as more serious diseases, such as the ongoing outbreak of coronavirus disease 2019 (COVID-19; formally known as 2019-nCoV). Coronaviruses can spread from animals to humans; symptoms include fever, cough, shortness of breath, and breathing difficulties; in more severe cases, infection can lead to death. This feed covers recent research on COVID-19.

Blastomycosis

Blastomycosis fungal infections spread through inhaling Blastomyces dermatitidis spores. Discover the latest research on blastomycosis fungal infections here.

Nuclear Pore Complex in ALS/FTD

Alterations in nucleocytoplasmic transport, controlled by the nuclear pore complex, may be involved in the pathomechanism underlying multiple neurodegenerative diseases including Amyotrophic Lateral Sclerosis and Frontotemporal Dementia. Here is the latest research on the nuclear pore complex in ALS and FTD.

Applications of Molecular Barcoding

The concept of molecular barcoding is that each original DNA or RNA molecule is attached to a unique sequence barcode. Sequence reads having different barcodes represent different original molecules, while sequence reads having the same barcode are results of PCR duplication from one original molecule. Discover the latest research on molecular barcoding here.

Chronic Fatigue Syndrome

Chronic fatigue syndrome is a disease characterized by unexplained disabling fatigue; the pathology of which is incompletely understood. Discover the latest research on chronic fatigue syndrome here.

Evolution of Pluripotency

Pluripotency refers to the ability of a cell to develop into three primary germ cell layers of the embryo. This feed focuses on the mechanisms that underlie the evolution of pluripotency. Here is the latest research.

Position Effect Variegation

Position Effect Variagation occurs when a gene is inactivated due to its positioning near heterochromatic regions within a chromosome. Discover the latest research on Position Effect Variagation here.

STING Receptor Agonists

Stimulator of IFN genes (STING) are a group of transmembrane proteins that are involved in the induction of type I interferon that is important in the innate immune response. The stimulation of STING has been an active area of research in the treatment of cancer and infectious diseases. Here is the latest research on STING receptor agonists.

Microbicide

Microbicides are products that can be applied to vaginal or rectal mucosal surfaces with the goal of preventing, or at least significantly reducing, the transmission of sexually transmitted infections. Here is the latest research on microbicides.