Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Review Article
  • Published:

Structural and functional insights into the epigenetic regulator MRG15

Acta Pharmacologica Sinica volume 45, pages 879–889 (2024)Cite this article

Abstract

MORF4-related gene on chromosome 15 (MRG15), a chromatin remodeller, is evolutionally conserved and ubiquitously expressed in mammalian tissues and cells. MRG15 plays vital regulatory roles in DNA damage repair, cell proliferation and division, cellular senescence and apoptosis by regulating both gene activation and gene repression via associations with specific histone acetyltransferase and histone deacetylase complexes. Recently, MRG15 has also been shown to rhythmically regulate hepatic lipid metabolism and suppress carcinoma progression. The unique N-terminal chromodomain and C-terminal MRG domain in MRG15 synergistically regulate its interaction with different cofactors, affecting its functions in various cell types. Thus, how MRG15 elaborately regulates target gene expression and performs diverse functions in different cellular contexts is worth investigating. In this review, we provide an in-depth discussion of how MRG15 controls multiple physiological and pathological processes.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Fig. 1: The crystal structures of human MRG15 and its MRG domain and chromodomain.
Fig. 2: The structural features of MRG family members.
Fig. 3: MRG15-related nuclear protein complexes.
Fig. 4: The roles of MRG15 in physiological and pathological processes.

Similar content being viewed by others

Data availability

The following PDB datasets were used in Fig. 1: 8C60, 2F5J, 2F5K. Mentioned PDB structural datasets are publicly available free of charge. Figure 4 was created with BioRender.com (Agreement number: BP2619NB1L).

References

  1. Bertram MJ, Pereira-Smith OM. Conservation of the MORF4 related gene family: identification of a new chromo domain subfamily and novel protein motif. Gene. 2001;266:111–21.

    Article  CAS  PubMed  Google Scholar 

  2. Bertram MJ, Berube NG, Hang-Swanson X, Ran Q, Leung JK, Bryce S, et al. Identification of a gene that reverses the immortal phenotype of a subset of cells and is a member of a novel family of transcription factor-like genes. Mol Cell Biol. 1999;19:1479–85.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. Tominaga K, Tominaga E, Ausserlechner MJ, Pereira-Smith OM. The cell senescence inducing gene product MORF4 is regulated by degradation via the ubiquitin/proteasome pathway. Exp Cell Res. 2010;316:92–102.

    Article  CAS  PubMed  Google Scholar 

  4. Leung JK, Pereira-Smith OM. Identification of genes involved in cell senescence and immortalization: potential implications for tissue ageing. Novartis Found Symp. 2001;235:105–10. discussion 110-5; 146-9

    Article  CAS  PubMed  Google Scholar 

  5. Tominaga K, Matzuk MM, Pereira-Smith OM. MrgX is not essential for cell growth and development in the mouse. Mol Cell Biol. 2005;25:4873–80.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Tominaga K, Leung JK, Rookard P, Echigo J, Smith JR, Pereira-Smith OM. MRGX is a novel transcriptional regulator that exhibits activation or repression of the B-myb promoter in a cell type-dependent manner. J Biol Chem. 2003;278:49618–24.

    Article  CAS  PubMed  Google Scholar 

  7. Kuo WY, Wu CY, Hwu L, Lee JS, Tsai CH, Lin KP, et al. Enhancement of tumor initiation and expression of KCNMA1, MORF4L2 and ASPM genes in the adenocarcinoma of lung xenograft after vorinostat treatment. Oncotarget. 2015;6:8663–75.

    Article  PubMed  PubMed Central  Google Scholar 

  8. Kooblall KG, Stokes VJ, Shariq OA, English KA, Stevenson M, Broxholme J, et al. miR-3156-5p is downregulated in serum of MEN1 patients and regulates expression of MORF4L2. Endocr Relat Cancer. 2022;29:557–68.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  9. Tominaga K, Pereira-Smith OM. The genomic organization, promoter position and expression profile of the mouse MRG15 gene. Gene. 2002;294:215–24.

    Article  CAS  PubMed  Google Scholar 

  10. Zhang P, Zhao J, Wang B, Du J, Lu Y, Chen J, et al. The MRG domain of human MRG15 uses a shallow hydrophobic pocket to interact with the N-terminal region of PAM14. Protein Sci. 2006;15:2423–34.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Kadlec J, Hallacli E, Lipp M, Holz H, Sanchez-Weatherby J, Cusack S, et al. Structural basis for MOF and MSL3 recruitment into the dosage compensation complex by MSL1. Nat Struct Mol Biol. 2011;18:142–9.

    Article  CAS  PubMed  Google Scholar 

  12. Xie T, Zmyslowski AM, Zhang Y, Radhakrishnan I. Structural basis for multi-specificity of MRG domains. Structure. 2015;23:1049–57.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. Xie T, Graveline R, Kumar GS, Zhang Y, Krishnan A, David G, et al. Structural basis for molecular interactions involving MRG domains: implications in chromatin biology. Structure. 2012;20:151–60.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Bowman BR, Moure CM, Kirtane BM, Welschhans RL, Tominaga K, Pereira-Smith OM, et al. Multipurpose MRG domain involved in cell senescence and proliferation exhibits structural homology to a DNA-interacting domain. Structure. 2006;14:151–8.

    Article  CAS  PubMed  Google Scholar 

  15. Wan MSM, Muhammad R, Koliopoulos MG, Roumeliotis TI, Choudhary JS, Alfieri C. Mechanism of assembly, activation and lysine selection by the SIN3B histone deacetylase complex. Nat Commun. 2023;14:2556.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  16. Redington J, Deveryshetty J, Kanikkannan L, Miller I, Korolev S. Structural insight into the mechanism of PALB2 interaction with MRG15. Genes (Basel). 2021;12:2002.

    Article  CAS  PubMed  Google Scholar 

  17. Zhang P, Du J, Sun B, Dong X, Xu G, Zhou J, et al. Structure of human MRG15 chromo domain and its binding to Lys36-methylated histone H3. Nucleic Acids Res. 2006;34:6621–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Eissenberg JC. Structural biology of the chromodomain: form and function. Gene. 2012;496:69–78.

    Article  CAS  PubMed  Google Scholar 

  19. Ito S, Kayukawa N, Ueda T, Taniguchi H, Morioka Y, Hongo F, et al. MRGBP promotes AR-mediated transactivation of KLK3 and TMPRSS2 via acetylation of histone H2A.Z in prostate cancer cells. Biochim Biophys Acta Gene Regul Mech. 2018;1861:794–802.

    Article  CAS  Google Scholar 

  20. Kumar GS, Chang W, Xie T, Patel A, Zhang Y, Wang GG, et al. Sequence requirements for combinatorial recognition of histone H3 by the MRG15 and Pf1 subunits of the Rpd3S/Sin3S corepressor complex. J Mol Biol. 2012;422:519–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Leung JK, Berube N, Venable S, Ahmed S, Timchenko N, Pereira-Smith OM. MRG15 activates the B-myb promoter through formation of a nuclear complex with the retinoblastoma protein and the novel protein PAM14. J Biol Chem. 2001;276:39171–8.

    Article  CAS  PubMed  Google Scholar 

  22. Pardo PS, Leung JK, Lucchesi JC, Pereira-Smith OM. MRG15, a novel chromodomain protein, is present in two distinct multiprotein complexes involved in transcriptional activation. J Biol Chem. 2002;277:50860–6.

    Article  CAS  PubMed  Google Scholar 

  23. Sakai K, Kitagawa Y, Saiki S, Saiki M, Hirose G. Effect of a paraneoplastic cerebellar degeneration-associated neural protein on B-myb promoter activity. Neurobiol Dis. 2004;15:529–33.

    Article  CAS  PubMed  Google Scholar 

  24. Jelinic P, Pellegrino J, David G. A novel mammalian complex containing Sin3B mitigates histone acetylation and RNA polymerase II progression within transcribed loci. Mol Cell Biol. 2011;31:54–62.

    Article  CAS  PubMed  Google Scholar 

  25. Hayakawa T, Ohtani Y, Hayakawa N, Shinmyozu K, Saito M, Ishikawa F, et al. RBP2 is an MRG15 complex component and down-regulates intragenic histone H3 lysine 4 methylation. Genes Cells. 2007;12:811–26.

    Article  CAS  PubMed  Google Scholar 

  26. Kumar GS, Xie T, Zhang Y, Radhakrishnan I. Solution structure of the mSin3A PAH2-Pf1 SID1 complex: a Mad1/Mxd1-like interaction disrupted by MRG15 in the Rpd3S/Sin3S complex. J Mol Biol. 2011;408:987–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. Peña AN, Tominaga K, Pereira-Smith OM. MRG15 activates the cdc2 promoter via histone acetylation in human cells. Exp Cell Res. 2011;317:1534–40.

    Article  PubMed  PubMed Central  Google Scholar 

  28. Garcia SN, Kirtane BM, Podlutsky AJ, Pereira-Smith OM, Tominaga K. Mrg15 null and heterozygous mouse embryonic fibroblasts exhibit DNA-repair defects post exposure to gamma ionizing radiation. FEBS Lett. 2007;581:5275–81.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  29. Cheng X, Cote J. A new companion of elongating RNA Polymerase II: TINTIN, an independent sub-module of NuA4/TIP60 for nucleosome transactions. Transcription. 2014;5:e995571.

    Article  PubMed  Google Scholar 

  30. Doyon Y, Selleck W, Lane WS, Tan S, Cote J. Structural and functional conservation of the NuA4 histone acetyltransferase complex from yeast to humans. Mol Cell Biol. 2004;24:1884–96.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  31. Gowher H, Brick K, Camerini-Otero RD, Felsenfeld G. Vezf1 protein binding sites genome-wide are associated with pausing of elongating RNA polymerase II. Proc Natl Acad Sci USA. 2012;109:2370–5.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  32. Devoucoux M, Roques C, Lachance C, Lashgari A, Joly-Beauparlant C, Jacquet K, et al. MRG proteins are shared by multiple protein complexes with distinct functions. Mol Cell Proteom. 2022;21:100253.

    Article  CAS  Google Scholar 

  33. Sy SM, Huen MS, Chen J. MRG15 is a novel PALB2-interacting factor involved in homologous recombination. J Biol Chem. 2009;284:21127–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  34. Hayakawa T, Zhang F, Hayakawa N, Ohtani Y, Shinmyozu K, Nakayama J, et al. MRG15 binds directly to PALB2 and stimulates homology-directed repair of chromosomal breaks. J Cell Sci. 2010;123:1124–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  35. Bleuyard JY, Fournier M, Nakato R, Couturier AM, Katou Y, Ralf C, et al. MRG15-mediated tethering of PALB2 to unperturbed chromatin protects active genes from genotoxic stress. Proc Natl Acad Sci USA. 2017;114:7671–6.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Martrat G, Maxwell CM, Tominaga E, Porta-de-la-Riva M, Bonifaci N, Gómez-Baldó L, et al. Exploring the link between MORF4L1 and risk of breast cancer. Breast Cancer Res. 2011;13:R40.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  37. Murr R, Loizou JI, Yang YG, Cuenin C, Li H, Wang ZQ, et al. Histone acetylation by Trrap-Tip60 modulates loading of repair proteins and repair of DNA double-strand breaks. Nat Cell Biol. 2006;8:91–9.

    Article  CAS  PubMed  Google Scholar 

  38. Kusch T, Florens L, Macdonald WH, Swanson SK, Glaser RL, Yates JR 3rd, et al. Acetylation by Tip60 is required for selective histone variant exchange at DNA lesions. Science. 2004;306:2084–7.

    Article  CAS  PubMed  Google Scholar 

  39. Frio TRio, Haanpaa M, Pouchet C, Pylkas K, Vuorela M, Tischkowitz M, et al. Mutation analysis of the gene encoding the PALB2-binding protein MRG15 in BRCA1/2-negative breast cancer families. J Hum Genet. 2010;55:842–3.

    Article  CAS  Google Scholar 

  40. Schmahling S, Meiler A, Lee Y, Mohammed A, Finkl K, Tauscher K, et al. Regulation and function of H3K36 di-methylation by the trithorax-group protein complex AMC. Development. 2018;145:dev163808.

    Article  PubMed  PubMed Central  Google Scholar 

  41. Huang C, Yang F, Zhang Z, Zhang J, Cai G, Li L, et al. Mrg15 stimulates Ash1 H3K36 methyltransferase activity and facilitates Ash1 Trithorax group protein function in Drosophila. Nat Commun. 2017;8:1649.

    Article  PubMed  PubMed Central  Google Scholar 

  42. Hou P, Huang C, Liu CP, Yang N, Yu T, Yin Y, et al. Structural insights into stimulation of Ash1L’s H3K36 methyltransferase activity through Mrg15 binding. Structure. 2019;27:837–45.

    Article  CAS  PubMed  Google Scholar 

  43. Lee Y, Yoon E, Cho S, Schmahling S, Muller J, Song JJ. Structural basis of MRG15-mediated activation of the ASH1l histone methyltransferase by releasing an autoinhibitory loop. Structure. 2019;27:846–52.

    Article  CAS  PubMed  Google Scholar 

  44. Al-Harthi S, Li H, Winkler A, Szczepski K, Deng J, Grembecka J, et al. MRG15 activates histone methyltransferase activity of ASH1L by recruiting it to the nucleosomes. Structure. 2023;31:1200–7.

    Article  CAS  PubMed  Google Scholar 

  45. Maritz C, Khaleghi R, Yancoskie MN, Diethelm S, Brulisauer S, Ferreira NS, et al. ASH1L-MRG15 methyltransferase deposits H3K4me3 and FACT for damage verification in nucleotide excision repair. Nat Commun. 2023;14:3892.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  46. Moshkin YM, Kan TW, Goodfellow H, Bezstarosti K, Maeda RK, Pilyugin M, et al. Histone chaperones ASF1 and NAP1 differentially modulate removal of active histone marks by LID-RPD3 complexes during NOTCH silencing. Mol Cell. 2009;35:782–93.

    Article  CAS  PubMed  Google Scholar 

  47. Wei Y, Tian C, Zhao Y, Liu X, Liu F, Li S, et al. MRG15 orchestrates rhythmic epigenomic remodelling and controls hepatic lipid metabolism. Nat Metab. 2020;2:447–60.

    Article  PubMed  Google Scholar 

  48. Chen M, Pereira-Smith OM, Tominaga K. Loss of the chromatin regulator MRG15 limits neural stem/progenitor cell proliferation via increased expression of the p21 Cdk inhibitor. Stem Cell Res. 2011;7:75–88.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Utley RT, Lacoste N, Jobin-Robitaille O, Allard S, Cote J. Regulation of NuA4 histone acetyltransferase activity in transcription and DNA repair by phosphorylation of histone H4. Mol Cell Biol. 2005;25:8179–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Pauty J, Rodrigue A, Couturier A, Buisson R, Masson JY. Exploring the roles of PALB2 at the crossroads of DNA repair and cancer. Biochem J. 2014;460:331–42.

    Article  CAS  PubMed  Google Scholar 

  51. Moyal L, Lerenthal Y, Gana-Weisz M, Mass G, So S, Wang SY, et al. Requirement of ATM-dependent monoubiquitylation of histone H2B for timely repair of DNA double-strand breaks. Mol Cell. 2011;41:529–42.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Wu J, Chen Y, Lu LY, Wu Y, Paulsen MT, Ljungman M, et al. Chfr and RNF8 synergistically regulate ATM activation. Nat Struct Mol Biol. 2011;18:761–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  53. Tominaga K, Kirtane B, Jackson JG, Ikeno Y, Ikeda T, Hawks C, et al. MRG15 regulates embryonic development and cell proliferation. Mol Cell Biol. 2005;25:2924–37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Zhang H, Li Y, Yang J, Tominaga K, Pereira-Smith OM, Tower J. Conditional inactivation of MRG15 gene function limits survival during larval and adult stages of Drosophila melanogaster. Exp Gerontol. 2010;45:825–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  55. Chen M, Takano-Maruyama M, Pereira-Smith OM, Gaufo GO, Tominaga K. MRG15, a component of HAT and HDAC complexes, is essential for proliferation and differentiation of neural precursor cells. J Neurosci Res. 2009;87:1522–31.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Humphrey GW, Wang YH, Hirai T, Padmanabhan R, Panchision DM, Newell LF, et al. Complementary roles for histone deacetylases 1, 2, and 3 in differentiation of pluripotent stem cells. Differentiation. 2008;76:348–56.

    Article  CAS  PubMed  Google Scholar 

  57. Kuzmochka C, Abdou HS, Hache RJG, Atlas E. Inactivation of histone deacetylase 1 (HDAC1) but not HDAC2 is required for the glucocorticoid-dependent CCAAT/enhancer-binding protein alpha (C/EBP alpha) expression and preadipocyte differentiation. Endocrinology. 2014;155:4762–73.

    Article  PubMed  Google Scholar 

  58. Streubel G, Fitzpatrick DJ, Oliviero G, Scelfo A, Moran B, Das S, et al. Fam60a defines a variant Sin3a-Hdac complex in embryonic stem cells required for self-renewal. EMBO J. 2017;36:2216–32.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  59. Sang Y, Zhang R, Sun L, Chen KK, Li SW, Xiong L, et al. MORF4L1 suppresses cell proliferation, migration and invasion by increasing p21 and E-cadherin expression in nasopharyngeal carcinoma. Oncol Lett. 2019;17:294–302.

    CAS  PubMed  Google Scholar 

  60. Chen Y, Li J, Dunn S, Xiong S, Chen W, Zhao Y, et al. Histone deacetylase 2 (HDAC2) protein-dependent deacetylation of mortality factor 4-like 1 (MORF4L1) protein enhances its homodimerization. J Biol Chem. 2014;289:7092–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Fujita M, Takasaki T, Nakajima N, Kawano T, Shimura Y, Sakamoto H. MRG-1, a mortality factor-related chromodomain protein, is required maternally for primordial germ cells to initiate mitotic proliferation in C. elegans. Mech Dev. 2002;114:61–9.

    Article  CAS  PubMed  Google Scholar 

  62. Gupta P, Leahul L, Wang X, Wang C, Bakos B, Jasper K, et al. Proteasome regulation of the chromodomain protein MRG-1 controls the balance between proliferative fate and differentiation in the C. elegans germ line. Development. 2015;142:291–302.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. Boije H, Ring H, Shirazi Fard S, Grundberg I, Nilsson M, Hallbook F. Alternative splicing of the chromodomain protein Morf4l1 pre-mRNA has implications on cell differentiation in the developing chicken retina. J Mol Neurosci. 2013;51:615–28.

    Article  CAS  PubMed  Google Scholar 

  64. Iwamori N, Tominaga K, Sato T, Riehle K, Iwamori T, Ohkawa Y, et al. MRG15 is required for pre-mRNA splicing and spermatogenesis. Proc Natl Acad Sci USA. 2016;113:E5408–15.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  65. Coppe JP, Desprez PY, Krtolica A, Campisi J. The senescence-associated secretory phenotype: the dark side of tumor suppression. Annu Rev Pathol-Mech. 2010;5:99–118.

    Article  CAS  Google Scholar 

  66. Liu X, Wei L, Dong Q, Liu L, Zhang MQ, Xie Z, et al. A large-scale CRISPR screen and identification of essential genes in cellular senescence bypass. Aging (Albany NY). 2019;11:4011–31.

    Article  CAS  PubMed  Google Scholar 

  67. Chen M, Tominaga K, Pereira-Smith OM. Emerging role of the MORF/MRG gene family in various biological processes, including aging. Ann N Y Acad Sci. 2010;1197:134–41.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  68. Graveline R, Marcinkiewicz K, Choi S, Paquet M, Wurst W, Floss T, et al. The chromatin-associated Phf12 protein maintains nucleolar integrity and prevents premature cellular senescence. Mol Cell Biol. 2017;37:e00522–16.

    Article  PubMed  PubMed Central  Google Scholar 

  69. Di Micco R, Sulli G, Dobreva M, Liontos M, Botrugno OA, Gargiulo G, et al. Interplay between oncogene-induced DNA damage response and heterochromatin in senescence and cancer. Nat Cell Biol. 2011;13:292–302.

    Article  PubMed  PubMed Central  Google Scholar 

  70. Liu DX, Greene LA. Regulation of neuronal survival and death by E2F-dependent gene repression and derepression. Neuron. 2001;32:425–38.

    Article  CAS  PubMed  Google Scholar 

  71. Liang Y, Lin JC, Wang K, Chen YJ, Liu HH, Luan R, et al. A nuclear ligand MRG15 involved in the proapoptotic activity of medicinal fungal galectin AAL (Agrocybe aegerita lectin). Biochim Biophys Acta. 2010;1800:474–80.

    Article  CAS  PubMed  Google Scholar 

  72. Zou C, Li J, Xiong S, Chen Y, Wu Q, Li X, et al. Mortality factor 4 like 1 protein mediates epithelial cell death in a mouse model of pneumonia. Sci Transl Med. 2015;7:311ra171.

    Article  PubMed  PubMed Central  Google Scholar 

  73. Huichalaf C, Sakai K, Jin B, Jones K, Wang GL, Schoser B, et al. Expansion of CUG RNA repeats causes stress and inhibition of translation in myotonic dystrophy 1 (DM1) cells. FASEB J. 2010;24:3706–19.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  74. Porras-Yakushi TR, Reitsma JM, Sweredoski MJ, Deshaies RJ, Hess S. In-depth proteomic analysis of proteasome inhibitors bortezomib, carfilzomib and MG132 reveals that mortality factor 4-like 1 (MORF4L1) protein ubiquitylation is negatively impacted. J Proteom. 2021;241:104197.

    Article  CAS  Google Scholar 

  75. Liao H, Liu XJ, Blank JL, Bouck DC, Bernard H, Garcia K, et al. Quantitative proteomic analysis of cellular protein modulation upon inhibition of the NEDD8-activating enzyme by MLN4924. Mol Cell Proteom. 2011;10:M111.009183.

    Article  Google Scholar 

  76. Tian C, Min X, Zhao Y, Wang Y, Wu X, Liu S, et al. MRG15 aggravates non-alcoholic steaohepatitis progression by regulating the mitochondrial proteolytic degradation of TUFM. J Hepatol. 2022;77:1491–503.

    Article  CAS  PubMed  Google Scholar 

  77. Bade D, Cai Q, Li L, Yu K, Dai X, Miao W, et al. Modulation of N-terminal methyltransferase 1 by an N6-methyladenosine-based epitranscriptomic mechanism. Biochem Biophys Res Commun. 2021;546:54–58.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. Baytek G, Blume A, Demirel FG, Bulut S, Popp O, Mertins P, et al. SUMOylation of the chromodomain factor MRG-1 in C. elegans affects chromatin-regulatory dynamics. Biotechniques. 2022;73:5–17.

    Article  CAS  PubMed  Google Scholar 

  79. Chen W, Salto-Tellez M, Palanisamy N, Ganesan K, Hou Q, Tan LK, et al. Targets of genome copy number reduction in primary breast cancers identified by integrative genomics. Genes Chromosomes Cancer. 2007;46:288–301.

    Article  CAS  PubMed  Google Scholar 

  80. Vietri MT, Caliendo G, Schiano C, Casamassimi A, Molinari AM, Napoli C, et al. Analysis of PALB2 in a cohort of Italian breast cancer patients: identification of a novel PALB2 truncating mutation. Fam Cancer. 2015;14:341–8.

    Article  CAS  PubMed  Google Scholar 

  81. Bhat-Nakshatri P, Kumar B, Simpson E, Ludwig KK, Cox ML, Gao H, et al. Breast cancer cell detection and characterization from breast milk-derived cells. Cancer Res. 2020;80:4828–39.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  82. Quinet A, Vindigni A. Superfast DNA replication causes damage in cancer cells. Nature. 2018;559:186–7.

    Article  CAS  PubMed  Google Scholar 

  83. Hashimoto Y, Ray Chaudhuri A, Lopes M, Costanzo V. Rad51 protects nascent DNA from Mre11-dependent degradation and promotes continuous DNA synthesis. Nat Struct Mol Biol. 2010;17:1305–11.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  84. Kadamb R, Leibovitch BA, Farias EF, Dahiya N, Suryawanshi H, Bansal N, et al. Invasive phenotype in triple negative breast cancer is inhibited by blocking SIN3A-PF1 interaction through KLF9 mediated repression of ITGA6 and ITGB1. Transl Oncol. 2022;16:101320.

    Article  CAS  PubMed  Google Scholar 

  85. Sanidas I, Polytarchou C, Hatziapostolou M, Ezell SA, Kottakis F, Hu L, et al. Phosphoproteomics screen reveals akt isoform-specific signals linking RNA processing to lung cancer. Mol Cell. 2014;53:577–90.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  86. Qin D, Zhao Y, Guo Q, Zhu S, Zhang S, Min L. Detection of pancreatic ductal adenocarcinoma by a qPCR-based normalizer-free circulating extracellular vesicles RNA signature. J Cancer. 2021;12:1445–54.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  87. Friedman SL, Neuschwander-Tetri BA, Rinella M, Sanyal AJ. Mechanisms of NAFLD development and therapeutic strategies. Nat Med. 2018;24:908–22.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. Schlegel MK, Janas MM, Jiang Y, Barry JD, Davis W, Agarwal S, et al. From bench to bedside: Improving the clinical safety of GalNAc-siRNA conjugates using seed-pairing destabilization. Nucleic Acids Res. 2022;50:6656–70.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. Matsuoka Y, Matsuoka Y, Shibata S, Ban T, Toratani N, Shigekawa M, et al. A chromodomain-containing nuclear protein, MRG15 is expressed as a novel type of dendritic mRNA in neurons. Neurosci Res. 2002;42:299–308.

    Article  CAS  PubMed  Google Scholar 

  90. Hajduskova M, Baytek G, Kolundzic E, Gosdschan A, Kazmierczak M, Ofenbauer A, et al. MRG-1/MRG15 is a barrier for germ cell to neuron reprogramming in Caenorhabditis elegans. Genetics. 2019;211:121–39.

    Article  CAS  PubMed  Google Scholar 

  91. Raina AK, Pardo P, Rottkamp CA, Zhu X, Pereira-Smith OM, Smith MA. Neurons in Alzheimer disease emerge from senescence. Mech Ageing Dev. 2001;123:3–9.

    Article  CAS  PubMed  Google Scholar 

  92. Reilly MP, Li MY, He J, Ferguson JF, Stylianou IM, Mehta NN, et al. Identification of ADAMTS7 as a novel locus for coronary atherosclerosis and association of ABO with myocardial infarction in the presence of coronary atherosclerosis: two genome-wide association studies. Lancet. 2011;377:383–92.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  93. Kessler T, Zhang L, Liu ZY, Yin XK, Huang YQ, Wang YB, et al. ADAMTS-7 inhibits re-endothelialization of injured arteries and promotes vascular remodeling through cleavage of thrombospondin-1. Circulation. 2015;131:1203–13.

    Article  Google Scholar 

  94. Bauer RC, Tohyama J, Cui J, Cheng L, Yang J, Zhang X, et al. Knockout of Adamts7, a novel coronary artery disease locus in humans, reduces atherosclerosis in mice. Circulation. 2015;131:1202. 

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  95. C. Coronary Artery Disease Genetics. A genome-wide association study in Europeans and South Asians identifies five new loci for coronary artery disease. Nat Genet. 2011;43:339–44.

    Article  Google Scholar 

  96. Schunkert H, Konig IR, Kathiresan S, Reilly MP, Assimes TL, Holm H, et al. Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet. 2011;43:333–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  97. Luco RF, Pan Q, Tominaga K, Blencowe BJ, Pereira-Smith OM, Misteli T. Regulation of alternative splicing by histone modifications. Science. 2010;327:996–1000.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by General Program of Shanghai Natural Science Foundation (22ZR1415100), the Major Program (82220108020, 92068202) of the National Natural Science Foundation of China, and the Program of Shanghai Academic/Technology Research Leader (20XD1400600). We apologize to all those whose work we have been unable to include due to space limitations.

Author information

Authors and Affiliations

  1. Department of Physiology and Pathophysiology, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China

    Nan Jiang, Yong-bo Li, Jia-yu Jin, Jie-yu Guo, Dan Meng & Xiu-ling Zhi

  2. CAS Key Laboratory of Nutrition, Metabolism and Food Safety, Shanghai Institute of Nutrition and Health, University of Chinese Academy of Sciences, Chinese Academy of Sciences, Shanghai, 200031, China

    Qiu-rong Ding

Authors
  1. Nan Jiang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Yong-bo Li
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Jia-yu Jin
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Jie-yu Guo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Qiu-rong Ding
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Dan Meng
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Xiu-ling Zhi
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Dan Meng or Xiu-ling Zhi.

Ethics declarations

Competing interests

The authors declare no competing interests.

Rights and permissions

Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Jiang, N., Li, Yb., Jin, Jy. et al. Structural and functional insights into the epigenetic regulator MRG15. Acta Pharmacol Sin 45, 879–889 (2024). https://doi.org/10.1038/s41401-023-01211-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/s41401-023-01211-6

Keywords

Search

Advanced search

Quick links