HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle (original) (raw)

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Sequence Read Archive

Data deposits

ChIP-Seq and RNA-Seq data from this study are available from the Sequence Read Archive (SRA) database (http://www.ncbi.nlm.nih.gov/sra) under the accession number SRP011927.

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Acknowledgements

We are grateful to the individuals and families with Cornelia de Lange syndrome who participated in this study, as well as to the referring physicians and colleagues who have contributed samples and clinical information. We thank Riken Omics Science Center, K. Nakagawa, S. Watanabe, M. Albrecht and J. Eckhold for technical support. We thank J.-M. Peters for the sororin and RAD21 antibodies. We thank F. Beckouët and K. Nasmyth for sharing unpublished results. We are indebted to the continued support of the US and International Cornelia de Lange Syndrome Foundations. This work was supported by National Institutes of Health grants K08HD055488 (NICHD, M.A.D.), GM49758 (D.W.C.) and P01 HD052860 (NICHD; I.D.K.), research grants from the US CdLS Foundation, institutional funds from the Children’s Hospital of Philadelphia, Intramural funding from the University of Lübeck (Schwerpunktprogramm, Medizinische Genetik: Von seltenen Varianten zur Krankheitsentstehung; F.J.K., G.G.-K.), Research Program of Innovative Cell Biology by Innovative Technology, Grant-in-Aid for Scientific Research (S) and for innovative science from MEXT (K.Sh.).

Author information

Author notes

  1. Matthew A. Deardorff, Masashige Bando, Ryuichiro Nakato and Erwan Watrin: These authors contributed equally to this work.

Authors and Affiliations

  1. Division of Human Genetics and Molecular Biology, The Children’s Hospital of Philadelphia, 19104, Pennsylvania, USA
    Matthew A. Deardorff, Dinah Clark, Sarah Ernst, Lauren J. Francey, Melanie Hullings, Maninder Kaur, Jonathan J. Wilde, Laird G. Jackson & Ian D. Krantz
  2. The Department of Pediatrics, University of Pennsylvania Perelman School of Medicine, Philadelphia, 19104, Pennsylvania, USA
    Matthew A. Deardorff & Ian D. Krantz
  3. Research Center for Epigenetic Disease, Institute for Molecular and Cellular Biosciences, The University of Tokyo, Tokyo 113-0032, Japan ,
    Masashige Bando, Ryuichiro Nakato, Masashi Minamino, Katsuya Saitoh, Makiko Komata, Yuki Katou & Katsuhiko Shirahige
  4. Centre National de la Recherche Scientifique (CNRS), Research Institute of Genetics and Development (IGDR), Faculté de Médecine, Rennes 35043, France ,
    Erwan Watrin, Christian Jaulin, Laura Magnaghi-Jaulin & Claude Prigent
  5. School and Graduate School of Bioscience and Biotechnology, Tokyo Institute of Technology, Yokohama 226-8503, Japan ,
    Takehiko Itoh
  6. Department of Chemistry, University of Pennsylvania, Philadelphia, 19104, Pennsylvania, USA
    Kathryn E. Cole, Christophe Decroos, Patrick M. Lombardi & David W. Christianson
  7. Center for Medical Genetics, Ghent University Hospital, 9000 Ghent, Belgium ,
    Elfride De Baere
  8. Institut für Klinische Genetik, Technische Universität Dresden, 01307 Dresden, Germany ,
    Nataliya Di Donato
  9. Department of Genetics, Institute of Child Health, 11527 Athens, Greece,
    Yolanda Gyftodimou & Michael B. Petersen
  10. Division of Molecular Biotherapy, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan,
    Kyotaro Hirashima & Hiroyuki Seimiya
  11. Department of Pathology, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan,
    Yuuichi Ishikawa
  12. Virology Division, National Cancer Center Research Institute, Tokyo 104-0045, Japan,
    Tohru Kiyono
  13. Department of Medical Genetics, Antwerp University Hospital and University of Antwerp, B-2650 Antwerp, Belgium,
    Geert R. Mortier
  14. Bio-Frontier Research Center, Tokyo Institute of Technology, Yokohama 226-8503, Japan ,
    Naohito Nozaki
  15. Department of Clinical Genetics, Aalborg Hospital, Aarhus University Hospital, 9100 Aalborg, Denmark,
    Michael B. Petersen
  16. Medical Genetics, University of Western Ontario, London, Ontario N6A 5W9, Canada ,
    Victoria M. Siu
  17. Graduate School of Frontier Sciences, The University of Tokyo, Tokyo 277-8561, Japan ,
    Yutaka Suzuki & Toru Hirota
  18. Experimental Pathology, Japanese Foundation for Cancer Research, Tokyo 135-8550, Japan ,
    Kentaro Takagaki
  19. GENDIA, 2020 Antwerp, Belgium ,
    Patrick J. Willems
  20. Institut für Humangenetik Lübeck, Universität zu Lübeck, 23538 Lübeck, Germany ,
    Gabriele Gillessen-Kaesbach & Frank J. Kaiser
  21. Department of Obstetrics and Gynecology, Drexel University School of Medicine, Philadelphia, 19102, Pennsylvania, USA
    Laird G. Jackson
  22. CREST, JST, K’s Gobancho, 7, Gobancho, Chiyoda-ku, Tokyo 102-0076, Japan ,
    Katsuhiko Shirahige

Authors

  1. Matthew A. Deardorff
  2. Masashige Bando
  3. Ryuichiro Nakato
  4. Erwan Watrin
  5. Takehiko Itoh
  6. Masashi Minamino
  7. Katsuya Saitoh
  8. Makiko Komata
  9. Yuki Katou
  10. Dinah Clark
  11. Kathryn E. Cole
  12. Elfride De Baere
  13. Christophe Decroos
  14. Nataliya Di Donato
  15. Sarah Ernst
  16. Lauren J. Francey
  17. Yolanda Gyftodimou
  18. Kyotaro Hirashima
  19. Melanie Hullings
  20. Yuuichi Ishikawa
  21. Christian Jaulin
  22. Maninder Kaur
  23. Tohru Kiyono
  24. Patrick M. Lombardi
  25. Laura Magnaghi-Jaulin
  26. Geert R. Mortier
  27. Naohito Nozaki
  28. Michael B. Petersen
  29. Hiroyuki Seimiya
  30. Victoria M. Siu
  31. Yutaka Suzuki
  32. Kentaro Takagaki
  33. Jonathan J. Wilde
  34. Patrick J. Willems
  35. Claude Prigent
  36. Gabriele Gillessen-Kaesbach
  37. David W. Christianson
  38. Frank J. Kaiser
  39. Laird G. Jackson
  40. Toru Hirota
  41. Ian D. Krantz
  42. Katsuhiko Shirahige

Contributions

M.B. and K.Sh. designed and performed the biochemical analyses; M.B., E.W., C.J., L.M.-J. and K.Sh. performed HDAC screening. M.B., K.Sa., E.W. and L.M.-J. performed chromatin spreading assays; N.N. monoclonal isolation; M.B., R.N., T.I., M.K., Y.K. and K.Sh. the ChIP sequencing and analysis; M.B., R.N. and Y.S. RNA sequencing; M.M., K.T. and T.H. microscopy. M.A.D., G.G.-K., L.G.J., F.J.K. and I.D.K. initiated the human studies. M.A.D., D.C., E.D.B., G.R.M., V.M.S., P.W., N.T., Y.G., M.B.P., G.G.-K. and I.D.K. identified and characterized clinical data. M.A.D., M.K., S.E., L.J.F., M.H. and F.J.K. performed mutation screening, inactivation and lymphoblastoid expression studies. K.H., T.K. and H.S. established fibroblast cell lines. M.A.D., J.J.W., K.E.C., P.M.L., C.D. and D.W.C. performed enzymatic and structural analysis. M.A.D., M.B. and K.Sh. drafted the manuscript. All authors analysed data, discussed the results and commented on the manuscript.

Corresponding authors

Correspondence toMatthew A. Deardorff, Ian D. Krantz or Katsuhiko Shirahige.

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Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Information (download PDF )

This file contains Supplementary Figures 1-10, a Supplementary Discussion, Supplementary Tables 1-6 and 8-9, Supplementary References and full scan images for all Western-blotting data presented in both the main article figures and supplementary figures. (PDF 5189 kb)

Supplementary Data (download XLS )

This file contains Nanostring data and calculations for 32-gene CdLS lymphoblastoid expression profiling. (XLS 174 kb)

Supplementary Data (download XLS )

This file contains Supplementary Table 7, which shows RNA sequencing data from Fibroblast experiments. (XLS 1594 kb)

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Deardorff, M., Bando, M., Nakato, R. et al. HDAC8 mutations in Cornelia de Lange syndrome affect the cohesin acetylation cycle.Nature 489, 313–317 (2012). https://doi.org/10.1038/nature11316

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