De novo missense variants in HDAC3 leading to epigenetic machinery dysfunction are associated with a variable neurodevelopmental disorder

(Yoon/Lim et al., American Journal of Human Genetics, 2024)

Our HDAC3 paper has been accepted for publication by the American Journal of Human Genetics! In this study, we investigated de novo HDAC3 variants associated with neurodevelopmental disorders. These variants exhibit impairments in HDAC activity, disruptions in protein-protein interactions, and abnormal cellular localization.

AJHG-D-24-00071R4_GA_edited_edited_edite

2024

30. Yoon JY, Lim SK, Seo H, Lee S, Cho J, Kim SY, Koh HY, Poduri AH, Ramakumaran V, Vasudevan P, de Groot MJ, Ko JM, Han D, Chae JH# and Lee CH#. (2024) De novo HDAC3 variants leading to epigenetic machinery dysfunction are associated with a neurodevelopmental disorder. American Journal of Human Genetics, Accepted

2023

29. Gracia-Diaz C, Zhou Y, Yang Q, ~, Lee CH, ~, Bhoj EJ, Martinez-Balbas MA, and Akizu N (2023) Gain and loss of function variants in EZH1 disrupt neurogenesis and cause dominant and recessive neurodevelopmental disorders. Nature Communications, 14(1):1409.

2022

28. Lee SH., Li YY., Kim HB., Eum SH., Park KM. and Lee CH., (2022) The role of EZH1 and EZH2 in development and cancer. BMB reports, 55(12):595-601.

27. Popoca L. and Lee CH. (2022) Techniques to study automethylation of histone methyltransferases and its functional impact. Methods in Molecular Biology, 2529, 109-120.

2021

26. Grau D., Zhang Y., Lee CH., Valencia-Sánchez M., Zhang J., Wang M., Holder M., Svetlov V., Tan, D., Nudler, E., Reinberg, D., Walz, T., and Armache, K-J. (2021) Structures of monomeric and dimeric PRC2:EZH1 reveal multiple surfaces that promote multivalent chromatin interactions. Nature Communications 12(714), https://doi.org/10.1038/s41467-020-20775-z.

25. Willcockson MA., Healton SE., Weiss CN., Bartholdy BA., Botbol Y., Mishra LN., Sidhwani DS., Wilson TJ., Pinto HB., Maron MI., Skalina KA., Toro LN., Zhao J., Lee CH., Hou H., Yusufova N., Meydan C., Osunsade A., David Y., Cesarman E., Melnick AM., Sidoli S., Garcia BA, Edelmann W., Macian F., Skoultchi AI. (2021) H1 histones control the epigenetic landscape by local chromatin compaction. Nature 589, 293–298.

2019

24. Lee CH., Yu JR., Granat J., Saldaña-Meyer R., Andrade J., LeRoy G., Jin Y., Lund P., Stafford JM., Garcia BA., Ueberheide B., Reinberg D. (2019) Automethylation of PRC2 promotes H3K27 methylation and is impaired in H3K27M pediatric glioma. Genes & Development 33(19-20),1428-1440.

23. LeRoy G., Oksuz O., Descostes N., Aoi Y., Ganai R., Ortabozkoyun H., Yu JR., Lee CH., Stafford JM., Shilatifard A., Reinberg D. (2019) LEDGF and HDGF2 relieve the nucleosome-induced barrier to transcription. Science Advances 5(10), eaay3068.

22. Yu JR., Lee CH., Oksuz O., Stafford JM., Reinberg D. (2019) PRC2 is high maintenance. Genes & Development 33(15-16), 903-935.

2018

21. Stafford JM., Lee CH., Voigt P., Descostes N., Saldaña-Meyer R., Yu JR., Leroy G., Oksuz O., Chapman JR., Suarez F., Modrek AS., Bayin NS., Placantonakis DG., Karajannis MA., Snuderl M., Ueberheide B., Reinberg D. (2018) Multiple modes of PRC2 inhibition elicit global chromatin alterations in H3K27M pediatric glioma. Science Advances 4(10), eaau5935.

20. Oksuz O., Narendra N., Lee CH., Descostes N., LeRoy G., Raviram R., Blumberg L., Karch K., Rocha PR., Garcia BA., Skok JA., Reinberg D. (2018) Capturing the onset of Polycomb domain formation. Molecular Cell 70(6), 1149-1162.

19. Lee CH., Holder M., Grau D., Saldaña-Meyer R., Yu JR., Ganai RA., Zhang J., Wang M., LeRoy G., Dobenecker MW., Reinberg D. †, Armache KJ.† (2018) Distinct stimulatory mechanisms regulate the catalytic activity of Polycomb Repressive Complex 2 (PRC2). Molecular Cell 70(3), 435-448.

18. Lee CH., Yu JR., Kumar S., Jin Y., LeRoy G., Bhanu N., Kaneko S., Garcia B.A., Hamilton AD., Reinberg D. (2018) Allosteric activation dictates PRC2 activity independent of its recruitment to chromatin. Molecular Cell 70(3), 422-434.

a. #18 and #19 are back-to-back papers in Molecular Cell.
b. #19 was selected by Dr. Cigall Kadoch (Harvard) for Faculty of 1000 (3 stars).

until 2017

17. Demin AA., Lee M, Lee CH., Seo YS. (2017) GSK-3β Homolog Rim11 and the Histone Deacetylase Complex Ume6-Sin3-Rpd3 Are Involved in Replication Stress Response Caused by Defects in Dna2. Genetics 206(2), 829-842.

16. Kwon B., Munashingha PR., Shin YK., Lee CH., Li B., Seo YS. (2016) Physical and functional interactions between nucleosomes and Rad27, a critical component of DNA processing during DNA metabolism. FEBS J. 283(23), 4247-4262.

15. Ruan C., Cui H., Lee CH., Li S., Li B. (2015) Homodimeric PHD-Domain containing Rco1 constitutes a critical signaling hub within the Rpd3S histone deacetylase complex. J Biol Chem 291(10), 5428-5438.

14. Ruan C., Lee CH., Cui H., Li S., Li B. (2015) Nucleosome contact triggers conformational changes of Rpd3S driving high affinity H3K36me engagement. Cell Reports 10(2), 204-215.

13. Lee M., Lee CH., Demin AA., Munashingha PR., Amangyeld T., Kwon B., Formosa T., Seo YS. (2014) Rad52/Rad59-dependent recombination as a means to rectify faulty Okazaki fragment processing. J Biol Chem. 289 (21), 15064-15079.

12. Lee CH., Wu, J., Li, B. (2013) Chromatin remodelers fine-tune H3K36me-directed deacetylation of neighbor nucleosomes by Rpd3S. Molecular Cell 52(2), 255-263.

11. Lee CH., Lee M., Kang HJ., Kim DH., Kang YH., Bae SH., and Seo YS. (2013) The N-terminal 45-kDa domain of Dna2 functions to target the Dna2 enzyme efficiently to secondary-structured DNA. J Biol Chem. 288(13), 9468-9481.

10. Huh JW., Wu J.*, Lee CH., Yun M., Gilada D., Brautigam CA., Li B. (2012) Multivalent di-nucleosome recognition enables the Rpd3S histone deacetylase complex to tolerate decreased H3K36 methylation levels. EMBO J. 31(17), 3564-3574.

9. Munashingha P.R., Lee CH., Kang YH., Shin YK., Nguyen TA., Seo YS. (2012) The trans-autostimulatory activity of Rad27 suppresses dna2 defects in Okazaki fragment processing. J Biol Chem. 287(12), 8675-8687.

8. Kang YH., Munashingha PR., Lee CH., Nguyen TA., Seo YS. (2011) Biochemical studies of the Saccharomyces cerevisiae Mph1 helicase on junction-containing DNA structures. Nucleic Acids Res. 40(5), 2089-2106.

7. Nguyen TA., Tak YS., Lee CH., Kang YH., Cho IT., Seo YS. (2011) Analysis of subunit assembly and function of the Saccharomyces cerevisiae RNase H2 complex. FEBS J. 278(24), 4927-4942.

6. Nguyen TA., Lee CH. and Seo YS. (2011) Lagging Strand Synthesis and Genomic Stability, DNA Repair - On the Pathways to Fixing DNA Damage and Errors, Dr. Francesca Storici (Ed.), ISBN: 978-953-307-649-2, InTech. (Book chapter)

5. Kang MJ., Lee CH., Kang YH., Cho IT., and Seo YS. (2010) Genetic and functional interaction between Mus81-Mms4 and Rad27. Nucleic Acids Res. 38(21), 7611-7625.

4. Lee CH., Shin YK., Phung TT., Bae JS., Kang YH., Nguyen TA., Kim JH., Kim DH., Kang MJ., Bae SH, and Seo YS. (2010) Involvement of Vts1, a structure-specific RNA-binding protein, in Okazaki fragment processing in yeast. Nucleic Acids Res. 38(5), 1583-1595.

3. Kang YH., Lee CH., and Seo YS. (2010) Dna2 on the road to Okazaki fragment processing and genome stability in eukaryotes. Crit Rev Biochem Mol Biol. 45(2), 71-96. 3574.

2. Cho IT., Kim DH., Kang YH., Lee CH., Amangyelid T., Nguyen TA., Hurwitz J., and Seo YS. (2009) Human replication factor C stimulates flap endonuclease 1. J Biol Chem. 284(16), 10387-10399.

1. Kang YH., Kang MJ., Kim JH., Lee CH., Cho IT., Hurwitz J., and Seo YS. (2009) The MPH1 gene of Saccharomyces cerevisiae functions in Okazaki fragment processing. J Biol Chem. 284(16), 10376-10386.