Please wait a minute...
Shopping Cart Email List Chinese
Advanced Search Fig/Tab
Protein & Cell

ISSN 1674-800X

ISSN 1674-8018(Online)

CN 11-5886/Q

Postal Subscription Code 80-984

2018 Impact Factor: 7.575

Featured Articles  |  Most Downloaded  |  Most Reading
Online Submission Subscribe to Our RSS Content Feed
Protein Cell    2023, Vol. 14 Issue (3) : 165-179    https://doi.org/10.1093/procel/pwac032
REVIEW
The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications
Yanjing Li1,2(), Kexue Ge1, Tingting Li1, Run Cai1, Yong Chen1()
1. State Key Laboratory of Molecular Biology, National Center for Protein Science Shanghai, Shanghai Institute of Biochemistry and Cell Biology, Center for Excellence in Molecular Cell Science, Chinese Academy of Sciences, 320 Yue Yang Road, Shanghai 200031, China
2. State Key Laboratory of Bioreactor Engineering, East China University of Science and Technology, Shanghai Collaborative Innovation Center for Biomanufacturing(SCICB), Meilong Road 130, Shanghai 200237, China
 Download: PDF(16499 KB)  
 Export: BibTeX | EndNote | Reference Manager | ProCite | RefWorks
Abstract

Histone lysine methyltransferases (HKMTs) deposit methyl groups onto lysine residues on histones and play important roles in regulating chromatin structure and gene expression. The structures and functions of HKMTs have been extensively investigated in recent decades, significantly advancing our understanding of the dynamic regulation of histone methylation. Here, we review the recent progress in structural studies of representative HKMTs in complex with nucleosomes (H3K4, H3K27, H3K36, H3K79, and H4K20 methyltransferases), with emphasis on the molecular mechanisms of nucleosome recognition and trans-histone crosstalk by these HKMTs. These structural studies inform HKMTs’ roles in tumorigenesis and provide the foundations for developing new therapeutic approaches targeting HKMTs in cancers.
Keywords nucleosome      cryo-EM structures      histone methyltransferases      epigenetics      histone methylation      tumorigenesis     
Corresponding Author(s): Yanjing Li,Yong Chen   
Issue Date: 17 April 2023
 Cite this article:   
Yanjing Li,Kexue Ge,Tingting Li, et al. The engagement of histone lysine methyltransferases with nucleosomes: structural basis, regulatory mechanisms, and therapeutic implications[J]. Protein Cell, 2023, 14(3): 165-179.
 URL:  
https://academic.hep.com.cn/pac/EN/10.1093/procel/pwac032
https://academic.hep.com.cn/pac/EN/Y2023/V14/I3/165
1 E Akoury , G Ma , S Demolin et al. Disordered region of H3K9 methyltransferase Clr4 binds the nucleosome and contributes to its activity. Nucleic Acids Res 2019; 47: 6726- 6736.
2 H Alam , M Tang , M Maitituoheti et al. KMT2D deficiency impairs super-enhancers to confer a glycolytic vulnerability in lung cancer. Cancer Cell 2020; 37: 599- 617.
3 CJ Anderson , MR Baird , A Hsu et al. Structural basis for recognition of ubiquitylated nucleosome by Dot1L methyltransferase. Cell Rep 2019; 26: 1681- 1690.
4 KI Ansari , S Kasiri , SS Mandal . Histone methylase MLL1 has critical roles in tumor growth and angiogenesis and its knockdown suppresses tumor growth in vivo. Oncogene 2013; 32: 3359- 3370.
5 A Ayoub , SH Park , YT Lee et al. Regulation of MLL1 methyltransferase activity in two distinct nucleosome binding modes. Biochemistry 2022; 61: 1- 9.
6 AJ Bannister , T Kouzarides . Regulation of chromatin by histone modifications. Cell Res 2011; 21: 381- 395.
7 S Beà , R Valdés-Mas , A Navarro et al. Landscape of somatic mutations and clonal evolution in mantle cell lymphoma. Proc Natl Acad Sci USA 2013; 110: 18250- 18255.
8 RL Bennett , A Swaroop , C Troche et al. The role of nuclear receptor-binding SET domain family histone lysine methyltransferases in cancer. Cold Spring Harb Perspect Med 2017; 7: a026708.
9 M Beringer , P Pisano , V Di Carlo et al. EPOP functionally links Elongin and Polycomb in pluripotent stem cells. Mol Cell 2016; 64: 645- 658.
10 KM Bernt , N Zhu , AU Sinha et al. MLL-rearranged leukemia is dependent on aberrant H3K79 methylation by DOT1L. Cancer Cell 2011; 20: 66- 78.
11 KP Bhat , H Ümit Kaniskan , J Jin et al. Epigenetics and beyond: targeting writers of protein lysine methylation to treat disease. Nat Rev Drug Discov 2021; 20: 265- 286.
12 S Bilokapic , M Halic . Nucleosome and ubiquitin position Set2 to methylate H3K36. Nat Commun 2019; 10: 3795.
13 JC Black , C Van Rechem , JR Whetstine . Histone lysine methylation dynamics: establishment, regulation, and biological impact. Mol Cell 2012; 48: 491- 507.
14 SD Briggs , T Xiao , ZW Sun et al. Gene silencing: trans-histone regulatory pathway in chromatin. Nature 2002; 418: 498.
15 A Brooun , KS Gajiwala , YL Deng et al. Polycomb repressive complex 2 structure with inhibitor reveals a mechanism of activation and drug resistance. Nat Commun 2016; 7: 11384.
16 R Cao , L Wang , H Wang et al. Role of histone H3 lysine 27 methylation in Polycomb-group silencing. Science 2002; 298: 1039- 1043.
17 F Cao , EC Townsend , H Karatas et al. Targeting MLL1 H3K4 methyltransferase activity in mixed-lineage leukemia. Mol Cell 2014; 53: 247- 261.
18 Y Chen , K Anastassiadis , A Kranz et al. MLL2, not MLL1, plays a major role in sustaining MLL-rearranged acute myeloid leukemia. Cancer Cell 2017; 31: 755- 770.
19 P Chi , CD Allis , GG Wang . Covalent histone modifications—miswritten, misinterpreted and mis-erased in human cancers. Nat Rev Cancer 2010; 10: 457- 469.
20 E Conway , E Jerman , E Healy et al. A family of vertebrate-specific Polycombs encoded by the LCOR/LCORL genes balance PRC2 subtype activities. Mol Cell 2018; 70: 408- 421.
21 JF Couture , E Collazo , JS Brunzelle et al. Structural and functional analysis of SET8, a histone H4 Lys-20 methyltransferase. Genes Dev 2005; 19: 1455- 1465.
22 JF Couture , LM Dirk , JS Brunzelle et al. Structural origins for the product specificity of SET domain protein methyltransferases. Proc Natl Acad Sci USA 2008; 105: 20659- 20664.
23 SR Daigle , EJ Olhava , CA Therkelsen et al. Selective killing of mixed lineage leukemia cells by a potent small-molecule DOT1L inhibitor. Cancer Cell 2011; 20: 53- 65.
24 SR Daigle , EJ Olhava , CA Therkelsen et al. Potent inhibition of DOT1L as treatment of MLL-fusion leukemia. Blood 2013; 122: 1017- 1025.
25 AJ Deshpande , L Chen , M Fazio et al. Leukemic transformation by the MLL-AF6 fusion oncogene requires the H3K79 methyltransferase Dot1l. Blood 2013; 121: 2533- 2541.
26 Y Dou , TA Milne , AJ Ruthenburg et al. Regulation of MLL1 H3K4 methyltransferase activity by its core components. Nat Struct Mol Biol 2006; 13: 713- 719.
27 HN Du , IM Fingerman , SD Briggs . Histone H3 K36 methylation is mediated by a trans-histone methylation pathway involving an interaction between Set2 and histone H4. Genes Dev 2008; 22: 2786- 2798.
28 G Duns , E van den Berg , I van Duivenbode et al. Histone methyltransferase gene SETD2 is a novel tumor suppressor gene in clear cell renal cell carcinoma. Cancer Res 2010; 70: 4287- 4291.
29 T Ernst , AJ Chase , J Score et al. Inactivating mutations of the histone methyltransferase gene EZH2 in myeloid disorders. Nat Genet 2010; 42: 722- 726.
30 RJ Fagan , AK Dingwall . COMPASS ascending: emerging clues regarding the roles of MLL3/KMT2C and MLL2/KMT2D proteins in cancer. Cancer Lett 2019; 458: 56- 65.
31 J Fang , Q Feng , CS Ketel et al. Purification and functional characterization of SET8, a nucleosomal histone H4-lysine 20-specific methyltransferase. Curr Biol 2002; 12: 1086- 1099.
32 Q Feng , H Wang , HH Ng et al. Methylation of H3-lysine 79 is mediated by a new family of HMTases without a SET domain. Curr Biol 2002; 12: 1052- 1058.
33 K Finogenova , J Bonnet , S Poepsel et al. Structural basis for PRC2 decoding of active histone methylation marks H3K36me2/3. Elife 2020; 9: e61964.
34 E Glancy , C Ciferri , AP Bracken . Structural basis for PRC2 engagement with chromatin. Curr Opin Struct Biol 2021; 67: 135- 144.
35 D Grau , Y Zhang , CH Lee et al. Structures of monomeric and dimeric PRC2:EZH1 reveal flexible modules involved in chromatin compaction. Nat Commun 2021; 12: 714.
36 S Hauri , F Comoglio , M Seimiya et al. A high-density map for navigating the human Polycomb complexome. Cell Rep 2016; 17: 583- 595.
37 MR Higgs , K Sato , JJ Reynolds et al. Histone methylation by SETD1A protects nascent DNA through the nucleosome chaperone activity of FANCD2. Mol Cell 2018; 71: 25- 41.
38 JM Hilden , PA Dinndorf , SO Meerbaum et al; Children’s Oncology Group. Analysis of prognostic factors of acute lymphoblastic leukemia in infants: report on CCG 1953 from the Children’s Oncology Group. Blood 2006; 108: 441- 451.
39 CH Ho , Y Takizawa , W Kobayashi et al. Structural basis of nucleosomal histone H4 lysine 20 methylation by SET8 methyltransferase. Life Sci Alliance 2021; 4: e202000919.
40 PL Hsu , H Li , HT Lau et al. Crystal structure of the COMPASS H3K4 methyltransferase catalytic module. Cell 2018; 174: 1106- 1116.
41 PL Hsu , H Shi , C Leonen et al. Structural basis of H2B ubiquitination-dependent H3K4 methylation by COMPASS. Mol Cell 2019; 76: 712- 723.
42 D Husmann , O Gozani . Histone lysine methyltransferases in biology and disease. Nat Struct Mol Biol 2019; 26: 880- 889.
43 M Imielinski , AH Berger , PS Hammerman et al. Mapping the hallmarks of lung adenocarcinoma with massively parallel sequencing. Cell 2012; 150: 1107- 1120.
44 JD Jaffe , Y Wang , HM Chan et al. Global chromatin profiling reveals NSD2 mutations in pediatric acute lymphoblastic leukemia. Nat Genet 2013; 45: 1386- 1391.
45 S Jang , C Kang , HS Yang et al. Structural basis of recognition and destabilization of the histone H2B ubiquitinated nucleosome by the DOT1L histone H3 Lys79 methyltransferase. Genes Dev 2019; 33: 620- 625.
46 A Janna , H Davarinejad , M Joshi et al. Structural paradigms in the recognition of the nucleosome core particle by histone lysine methyltransferases. Front Cell Dev Biol 2020; 8: 600.
47 L Jiao , X Liu . Structural basis of histone H3K27 trimethylation by an active polycomb repressive complex 2. Science 2015; 350: aac4383.
48 S Jørgensen , I Elvers , MB Trelle et al. The histone methyltransferase SET8 is required for S-phase progression. J Cell Biol 2007; 179: 1337- 1345.
49 N Justin , Y Zhang , C Tarricone et al. Structural basis of oncogenic histone H3K27M inhibition of human polycomb repressive complex 2. Nat Commun 2016; 7: 11316.
50 AA Kalashnikova , ME Porter-Goff , UM Muthurajan et al. The role of the nucleosome acidic patch in modulating higher order chromatin structure. J R Soc Interface 2013; 10: 20121022.
51 R Kalb , S Latwiel , HI Baymaz et al. Histone H2A monoubiquitination promotes histone H3 methylation in Polycomb repression. Nat Struct Mol Biol 2014; 21: 569- 571.
52 V Kasinath , C Beck , P Sauer et al. JARID2 and AEBP2 regulate PRC2 in the presence of H2AK119ub1 and other histone modifications. Science 2021; 371: eabc3393.
53 KH Kim , CW Roberts . Targeting EZH2 in cancer. Nat Med 2016; 22: 128- 134.
54 J Kim , M Guermah , RK McGinty et al. RAD6-mediated transcription-coupled H2B ubiquitylation directly stimulates H3K4 methylation in human cells. Cell 2009; 137: 459- 471.
55 J Kim , JA Kim , RK McGinty et al. The n-SET domain of Set1 regulates H2B ubiquitylation-dependent H3K4 methylation. Mol Cell 2013; 49: 1121- 1133.
56 T Kouzarides . Chromatin modifications and their function. Cell 2007; 128: 693- 705.
57 AV Krivtsov , SA Armstrong . MLL translocations, histone modifications and leukaemia stem-cell development. Nat Rev Cancer 2007; 7: 823- 833.
58 AV Krivtsov , T Hoshii , SA Armstrong . Mixed-lineage leukemia fusions and chromatin in leukemia. Cold Spring Harb Perspect Med 2017; 7: a026658.
59 N Lacoste , RT Utley , JM Hunter et al. Disruptor of telomeric silencing-1 is a chromatin-specific histone H3 methyltransferase. J Biol Chem 2002; 277: 30421- 30424.
60 UTF Lam , BKY Tan , JJX Poh et al. Structural and functional specificity of H3K36 methylation. Epigenetics Chromatin 2022; 15: 17.
61 C Larsson , L Cordeddu , L Siggens et al. Restoration of KMT2C/MLL3 in human colorectal cancer cells reinforces genome-wide H3K4me1 profiles and influences cell growth and gene expression. Clin Epigenetics 2020; 12: 74.
62 CH Lee , JR Yu , S Kumar et al. Allosteric activation dictates PRC2 activity independent of its recruitment to chromatin. Mol Cell 2018a; 70: 422- 434.
63 S Lee , S Oh , K Jeong et al. Dot1 regulates nucleosome dynamics by its inherent histone chaperone activity in yeast. Nat Commun 2018b; 9: 240.
64 YT Lee , A Ayoub , SH Park et al. Mechanism for DPY30 and ASH2L intrinsically disordered regions to modulate the MLL/SET1 activity on chromatin. Nat Commun 2021; 12: 2953.
65 F van Leeuwen , PR Gafken , DE Gottschling . Dot1p modulates silencing in yeast by methylation of the nucleosome core. Cell 2002; 109: 745- 756.
66 Y Li , J Jiao . Histone chaperone HIRA regulates neural progenitor cell proliferation and neurogenesis via β-catenin. J Cell Biol 2017; 216: 1975- 1992.
67 X Li , Y Song . Structure, function and inhibition of critical protein-protein interactions involving mixed lineage leukemia 1 and its fusion oncoproteins. J Hematol Oncol 2021b; 14: 56.
68 Y Li , J Han , Y Zhang et al. Structural basis for activity regulation of MLL family methyltransferases. Nature 2016; 530: 447- 452.
69 Y Li , L Zhao , X Tian et al. Crystal structure of MLL2 complex guides the identification of a methylation site on P53 catalyzed by KMT2 family methyltransferases. Structure 2020; 28: 1141- 1148.
70 W Li , W Tian , G Yuan et al. Molecular basis of nucleosomal H3K36 methylation by NSD methyltransferases. Nature 2021a; 590: 498- 503.
71 R Liefke , V Karwacki-Neisius , Y Shi . EPOP interacts with Elongin BC and USP7 to modulate the chromatin landscape. Mol Cell 2016; 64: 659- 672.
72 X Liu . A structural perspective on gene repression by Polycomb repressive complex 2. Subcell Biochem 2021; 96: 519- 562.
73 Y Liu , Y Zhang , H Xue et al. Cryo-EM structure of SETD2/Set2 methyltransferase bound to a nucleosome containing oncohistone mutations. Cell Discov 2021; 7: 32.
74 K Luger , AW Mäder , RK Richmond et al. Crystal structure of the nucleosome core particle at 2.8 A resolution. Nature 1997; 389: 251- 260.
75 R Margueron , D Reinberg . The Polycomb complex PRC2 and its mark in life. Nature 2011; 469: 343- 349.
76 C Martin , Y Zhang . The diverse functions of histone lysine methylation. Nat Rev Mol Cell Biol 2005; 6: 838- 849.
77 RK McGinty , J Kim , C Chatterjee et al. Chemically ubiquitylated histone H2B stimulates hDot1L-mediated intranucleosomal methylation. Nature 2008; 453: 812- 816.
78 J Min , Q Feng , Z Li et al. Structure of the catalytic domain of human DOT1L, a non-SET domain nucleosomal histone methyltransferase. Cell 2003; 112: 711- 723.
79 M Mohan , HM Herz , A Shilatifard . SnapShot: histone lysine methylase complexes. Cell 2012; 149: 498- 498.
80 RD Morin , NA Johnson , TM Severson et al. Somatic mutations altering EZH2 (Tyr641) in follicular and diffuse large B-cell lymphomas of germinal-center origin. Nat Genet 2010; 42: 181- 185.
81 G Nassa , A Salvati , R Tarallo et al. Inhibition of histone methyltransferase DOT1L silences ERα gene and blocks proliferation of antiestrogen-resistant breast cancer cells. Sci Adv 2019: 5: eaav5590.
82 TG Natarajan , BV Kallakury , CE Sheehan et al. Epigenetic regulator MLL2 shows altered expression in cancer cell lines and tumors from human breast and colon. Cancer Cell Int 2010; 10: 13.
83 HH Ng , Q Feng , H Wang et al. Lysine methylation within the globular domain of histone H3 by Dot1 is important for telomeric silencing and Sir protein association. Genes Dev 2002a; 16: 1518- 1527.
84 HH Ng , RM Xu , Y Zhang et al. Ubiquitination of histone H2B by Rad6 is required for efficient Dot1-mediated methylation of histone H3 lysine 79. J Biol Chem 2002b; 277: 34655- 34657.
85 K Nishioka , JC Rice , K Sarma et al. PR-Set7 is a nucleosome-specific methyltransferase that modifies lysine 20 of histone H4 and is associated with silent chromatin. Mol Cell 2002; 9: 1201- 1213.
86 H Oda , I Okamoto , N Murphy et al. Monomethylation of histone H4-lysine 20 is involved in chromosome structure and stability and is essential for mouse development. Mol Cell Biol 2009; 29: 2278- 2295.
87 Y Okada , Q Feng , Y Lin et al. hDOT1L links histone methylation to leukemogenesis. Cell 2005; 121: 167- 178.
88 AV Onufriev , H Schiessel . The nucleosome: from structure to function through physics. Curr Opin Struct Biol 2019; 56: 119- 130.
89 R Ouda , N Sarai , V Nehru et al. SPT6 interacts with NSD2 and facilitates interferon-induced transcription. FEBS Lett 2018; 592: 1681- 1692.
90 J Padeken , SP Methot , SM Gasser. Establishment of H3K9-methylated heterochromatin and its functions in tissue differentiation and maintenance. Nat Rev Mol Cell Biol 2022: 1- 18.
91 SH Park , A Ayoub , YT Lee et al. Cryo-EM structure of the human MLL1 core complex bound to the nucleosome. Nat Commun 2019; 10: 5540.
92 YK Park , JE Lee , Z Yan et al. Interplay of BAF and MLL4 promotes cell type-specific enhancer activation. Nat Commun 2021; 12: 1630.
93 A Patel , V Dharmarajan , VE Vought et al. On the mechanism of multiple lysine methylation by the human mixed lineage leukemia protein-1 (MLL1) core complex. J Biol Chem 2009; 284: 24242- 24256.
94 TC Petrossian , SG Clarke . Uncovering the human methyltransferasome. Mol Cell Proteom 2011; 10: M110.000976.
95 S Poepsel , V Kasinath , E Nogales . Cryo-EM structures of PRC2 simultaneously engaged with two functionally distinct nucleosomes. Nat Struct Mol Biol 2018; 25: 154- 162.
96 Q Qu , YH Takahashi , Y Yang et al. Structure and conformational dynamics of a COMPASS histone H3K4 methyltransferase complex. Cell 2018; 174: 1117- 1126. Rothbart SB, Baylin SB. Epigenetic therapy for epithelioid sarcoma. Cell 2020;181:211.
97 N Sarai , K Nimura , T Tamura et al. WHSC1 links transcription elongation to HIRA-mediated histone H3.3 deposition. EMBO J 2013; 32: 2392- 2406.
98 T Schalch , S Duda , DF Sargent et al. X-ray structure of a tetranucleosome and its implications for the chromatin fibre. Nature 2005; 436: 138- 141.
99 FW Schmitges , AB Prusty , M Faty et al. Histone methylation by PRC2 is inhibited by active chromatin marks. Mol Cell 2011; 42: 330- 341.
100 B Schuettengruber , HM Bourbon , L Di Croce et al. Genome regulation by Polycomb and Trithorax: 70 years and counting. Cell 2017; 171: 34- 57.
101 CJ Sneeringer , MP Scott , KW Kuntz et al. Coordinated activities of wild-type plus mutant EZH2 drive tumor-associated hypertrimethylation of lysine 27 on histone H3 (H3K27) in human B-cell lymphomas. Proc Natl Acad Sci USA 2010; 107: 20980- 20985.
102 F Song , P Chen , D Sun et al. Cryo-EM study of the chromatin fiber reveals a double helix twisted by tetranucleosomal units. Science 2014; 344: 376- 380.
103 BD Strahl , CD Allis . The language of covalent histone modifications. Nature 2000; 403: 41- 45.
104 BD Strahl , PA Grant , SD Briggs et al. Set2 is a nucleosomal histone H3-selective methyltransferase that mediates transcriptional repression. Mol Cell Biol 2002; 22: 1298- 1306.
105 ZW Sun , CD Allis . Ubiquitination of histone H2B regulates H3 methylation and gene silencing in yeast. Nature 2002; 418: 104- 108.
106 AT Thiel , P Blessington , T Zou et al. MLL-AF9-induced leukemogenesis requires coexpression of the wild-type Mll allele. Cancer Cell 2010; 17: 148- 159.
107 MI Valencia-Sánchez , P De Ioannes , M Wang et al. Structural basis of Dot1L stimulation by histone H2B lysine 120 ubiquitination. Mol Cell 2019; 74: 1010- 1019.
108 MI Valencia-Sánchez , P De Ioannes , M Wang et al. Regulation of the Dot1 histone H3K79 methyltransferase by histone H4K16 acetylation. Science 2021; 371: eabc6663.
109 R Vatapalli , V Sagar , Y Rodriguez et al. Histone methyltransferase DOT1L coordinates AR and MYC stability in prostate cancer. Nat Commun 2020; 11: 4153.
110 P Voigt , G LeRoy , WJ Drury 3rd et al. Asymmetrically modified nucleosomes. Cell 2012; 151: 181- 193.
111 EJ Wagner , PB Carpenter . Understanding the language of Lys36 methylation at histone H3. Nat Rev Mol Cell Biol 2012; 13: 115- 126.
112 EJ Worden , C Wolberger . Activation and regulation of H2B-Ubiquitindependent histone methyltransferases. Curr Opin Struct Biol 2019; 59: 98- 106.
113 EJ Worden , NA Hoffmann , CW Hicks et al. Mechanism of cross-talk between H2B ubiquitination and H3 methylation by Dot1L. Cell 2019; 176: 1490- 1501.
114 EJ Worden , X Zhang , C Wolberger . Structural basis for COMPASS recognition of an H2B-ubiquitinated nucleosome. Elife 2020; 9: e53199.
115 L Wu , SY Lee , B Zhou et al. ASH2L regulates ubiquitylation signaling to MLL: trans-regulation of H3 K4 methylation in higher eukaryotes. Mol Cell 2013; 49: 1108- 1120.
116 B Xiao , C Jing , G Kelly et al. Specificity and mechanism of the histone methyltransferase Pr-Set7. Genes Dev 2005; 19: 1444- 1454.
117 H Xue , T Yao , M Cao et al. Structural basis of nucleosome recognition and modification by MLL methyltransferases. Nature 2019; 573: 445- 449.
118 S Yang , X Zheng , C Lu et al. Molecular basis for oncohistone H3 recognition by SETD2 methyltransferase. Genes Dev 2016; 30: 1611- 1616.
119 T Yao , W Jing , Z Hu et al. Structural basis of the crosstalk between histone H2B monoubiquitination and H3 lysine 79 methylation on nucleosome. Cell Res 2019; 29: 330- 333.
120 DB Yap , J Chu , T Berg et al. Somatic mutations at EZH2 Y641 act dominantly through a mechanism of selectively altered PRC2 catalytic activity, to increase H3K27 trimethylation. Blood 2011; 117: 2451- 2459.
121 W Yuan , M Xu , C Huang et al. H3K36 methylation antagonizes PRC2-mediated H3K27 methylation. J Biol Chem 2011; 286: 7983- 7989.
122 W Yuan , T Wu , H Fu et al. Dense chromatin activates Polycomb repressive complex 2 to regulate H3 lysine 27 methylation. Science 2012; 337: 971- 975.
123 G Yuan , B Ma , W Yuan et al. Histone H2A ubiquitination inhibits the enzymatic activity of H3 lysine 36 methyltransferases. J Biol Chem 2013; 288: 30832- 30842.
124 X Zhai , JE Brownell . Biochemical perspectives on targeting KMT2 methyltransferases in cancer. Trends Pharmacol Sci 2021; 42: 688- 699.
125 J Zhang , D Dominguez-Sola , S Hussein et al. Disruption of KMT2D perturbs germinal center B cell development and promotes lymphomagenesis. Nat Med 2015a; 21: 1190- 1198.
126 Y Zhang , A Mittal , J Reid et al. Evolving catalytic properties of the MLL family SET domain. Structure 2015b; 23: 1921- 1933.
127 S Zhao , CD Allis , GG Wang . The language of chromatin modification in human cancers. Nat Rev Cancer 2021; 21: 413- 430.
128 JY Zheng , CY Wang , C Gao et al. MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity. Cell Death Dis 2021; 12: 364.
129 K Zhou , G Gaullier , K Luger . Nucleosome structure and dynamics are coming of age. Nat Struct Mol Biol 2019; 26: 3- 13.
130 J Zhu , MA Sammons , G Donahue et al. Gain-of-function p53 mutants co-opt chromatin pathways to drive cancer growth. Nature 2015; 525: 206- 211.
131 Q Zhu , L Fang , J Heuberger et al. The Wnt-driven Mll1 epigenome regulates salivary gland and head and neck cancer. Cell Rep 2019; 26: 415- 428.
[1] Linchong Sun, Huafeng Zhang, Ping Gao. Metabolic reprogramming and epigenetic modifications on the path to cancer[J]. Protein Cell, 2022, 13(12): 877-919.
[2] Yu-Kun Xia, Yi-Rong Zeng, Meng-Li Zhang, Peng Liu, Fang Liu, Hao Zhang, Chen-Xi He, Yi-Ping Sun, Jin-Ye Zhang, Cheng Zhang, Lei Song, Chen Ding, Yu-Jie Tang, Zhen Yang, Chen Yang, Pu Wang, Kun-Liang Guan, Yue Xiong, Dan Ye. Tumor-derived neomorphic mutations in ASXL1 impairs the BAP1-ASXL1-FOXK1/K2 transcription network[J]. Protein Cell, 2021, 12(7): 557-577.
[3] Yuliang Feng, Xingguo Liu, Siim Pauklin. 3D chromatin architecture and epigenetic regulation in cancer stem cells[J]. Protein Cell, 2021, 12(6): 440-454.
[4] Mona Teng, Stanley Zhou, Changmeng Cai, Mathieu Lupien, Housheng Hansen He. Pioneer of prostate cancer: past, present and the future of FOXA1[J]. Protein Cell, 2021, 12(1): 29-38.
[5] Qingfei Zheng, Igor Maksimovic, Akhil Upad, Yael David. Non-enzymatic covalent modifications: a new link between metabolism and epigenetics[J]. Protein Cell, 2020, 11(6): 401-416.
[6] Lin-Yong Zhao, Jinghui Song, Yibin Liu, Chun-Xiao Song, Chengqi Yi. Mapping the epigenetic modifications of DNA and RNA[J]. Protein Cell, 2020, 11(11): 792-808.
[7] Lili Yu, Kai-yuan Ji, Jian Zhang, Yanxia Xu, Yue Ying, Taoyi Mai, Shuxiang Xu, Qian-bing Zhang, Kai-tai Yao, Yang Xu. Core pluripotency factors promote glycolysis of human embryonic stem cells by activating GLUT1 enhancer[J]. Protein Cell, 2019, 10(9): 668-680.
[8] Youqin Xu, Kaiyuan Ji, Meng Wu, Bingtao Hao, Kai-tai Yao, Yang Xu. A miRNA-HERC4 pathway promotes breast tumorigenesis by inactivating tumor suppressor LATS1[J]. Protein Cell, 2019, 10(8): 595-605.
[9] Xiangxian Zhang, Li Liu, Xia Yuan, Yuquan Wei, Xiawei Wei. JMJD3 in the regulation of human diseases[J]. Protein Cell, 2019, 10(12): 864-882.
[10] Donglu Wu, Yong Cai, Jingji Jin. Potential coordination role between O-GlcNAcylation and epigenetics[J]. Protein Cell, 2017, 8(10): 713-723.
[11] Haley Vaseghi, Jiandong Liu, Li Qian. Molecular barriers to direct cardiac reprogramming[J]. Protein Cell, 2017, 8(10): 724-734.
[12] Kegan Zhu,Lei Liu,Junliang Zhang,Yanbo Wang,Hongwei Liang,Gentao Fan,Zhenhuan Jiang,Chen-Yu Zhang,Xi Chen,Guangxin Zhou. MiR-29b suppresses the proliferation and migration of osteosarcoma cells by targeting CDK6[J]. Protein Cell, 2016, 7(6): 434-444.
[13] Haiyang Zhang,Jingjing Duan,Yanjun Qu,Ting Deng,Rui Liu,Le Zhang,Ming Bai,Jialu Li,Tao Ning,Shaohua Ge,Xia Wang,Zhenzhen Wang,Qian Fan,Hongli Li,Guoguang Ying,Dingzhi Huang,Yi Ba. Onco-miR-24 regulates cell growth and apoptosis by targeting BCL2L11 in gastric cancer[J]. Protein Cell, 2016, 7(2): 141-151.
[14] Caiguo Zhang,Fan Zhang. Iron homeostasis and tumorigenesis: molecular mechanisms and therapeutic opportunities[J]. Protein Cell, 2015, 6(2): 88-100.
[15] David M. Roy,Logan A. Walsh,Timothy A. Chan. Driver mutations of cancer epigenomes[J]. Protein Cell, 2014, 5(4): 265-296.
Viewed
Full text


Abstract

Cited
  Shared   
  Discussed