7v0e › Citations

Structure of DNMT3B homo-oligomer reveals vulnerability to impairment by ICF mutations.

Gao L, Guo Y, Biswal M, Lu J, Yin J, Fang J, Chen X, Shao Z, Huang M, Wang Y, Wang GG, Song J
Nat Commun 13 4249 (2022)
Cited: 5 times
EuropePMC logo PMID: 35869095

Abstract

DNA methyltransferase DNMT3B plays an essential role in establishment of DNA methylation during embryogenesis. Mutations of DNMT3B are associated with human diseases, notably the immunodeficiency, centromeric instability and facial anomalies (ICF) syndrome. How ICF mutations affect DNMT3B activity is not fully understood. Here we report the homo-oligomeric structure of DNMT3B methyltransferase domain, providing insight into DNMT3B-mediated DNA methylation in embryonic stem cells where the functional regulator DNMT3L is dispensable. The interplay between one of the oligomer interfaces (FF interface) and the catalytic loop renders DNMT3B homo-oligomer a conformation and activity distinct from the DNMT3B-DNMT3L heterotetramer, and a greater vulnerability to certain ICF mutations. Biochemical and cellular analyses further reveal that the ICF mutations of FF interface impair the DNA binding and heterochromatin targeting of DNMT3B, leading to reduced DNA methylation in cells. Together, this study provides a mechanistic understanding of DNMT3B-mediated DNA methylation and its dysregulation in disease.

Articles - 7v0e mentioned but not cited (1)

  1. Structural basis for the allosteric regulation and dynamic assembly of DNMT3B. Lu J, Fang J, Zhu H, Liang KL, Khudaverdyan N, Song J. Nucleic Acids Res 51 12476-12491 (2023)


Reviews citing this publication (1)

  1. Epigenetic Targets in Schizophrenia Development and Therapy. Wawrzczak-Bargieła A, Bilecki W, Maćkowiak M. Brain Sci 13 426 (2023)

Articles citing this publication (3)

  1. Three's a crowd - why did three N-terminal methyltransferases evolve for one job? Conner MM, Schaner Tooley CE. J Cell Sci 136 jcs260424 (2023)
  2. Evaluation of Clinical and Immunological Alterations Associated with ICF Syndrome. Bilgic Eltan S, Nain E, Catak MC, Ezen E, Sefer AP, Karimi N, Kiykim A, Kolukisa B, Baser D, Bulutoglu A, Kasap N, Yorgun Altunbas M, Yalcin Gungoren E, Kendir Demirkol Y, Kutlug S, Hancioglu G, Dilek F, Yildiran A, Ozen A, Karakoc-Aydiner E, Erman B, Baris S. J Clin Immunol 44 26 (2023)
  3. TNRC18 engages H3K9me3 to mediate silencing of endogenous retrotransposons. Zhao S, Lu J, Pan B, Fan H, Byrum SD, Xu C, Kim A, Guo Y, Kanchi KL, Gong W, Sun T, Storey AJ, Burkholder NT, Mackintosh SG, Kuhlers PC, Edmondson RD, Strahl BD, Diao Y, Tackett AJ, Raab JR, Cai L, Song J, Wang GG. Nature 623 633-642 (2023)


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