Role of epigenetics in unicellular to multicellular transition in Dictyostelium.

Simon Yuan Wang, Elizabeth Ann Pollina, I-Hao Wang, Lindsay Kristina Pino, Henry L Bushnell, Ken Takashima, Colette Fritsche, George Sabin, Benjamin Aaron Garcia, Paul Lieberman Greer, Eric Lieberman Greer
Author Information
  1. Simon Yuan Wang: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  2. Elizabeth Ann Pollina: Department of Neurobiology, Harvard Medical School, Boston, MA, 02115, USA.
  3. I-Hao Wang: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  4. Lindsay Kristina Pino: Department of Biochemistry and Biophysics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  5. Henry L Bushnell: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  6. Ken Takashima: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  7. Colette Fritsche: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  8. George Sabin: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA.
  9. Benjamin Aaron Garcia: Department of Biochemistry and Biophysics, University of Pennsylvania, Perelman School of Medicine, Philadelphia, PA, 19104, USA.
  10. Paul Lieberman Greer: Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, MA, 01605, USA.
  11. Eric Lieberman Greer: Division of Newborn Medicine, Boston Children's Hospital, 300 Longwood Avenue, Boston, MA, 02115, USA. eric.greer@childrens.harvard.edu. ORCID

Abstract

BACKGROUND: The evolution of multicellularity is a critical event that remains incompletely understood. We use the social amoeba, Dictyostelium discoideum, one of the rare organisms that readily transits back and forth between both unicellular and multicellular stages, to examine the role of epigenetics in regulating multicellularity.
RESULTS: While transitioning to multicellular states, patterns of H3K4 methylation and H3K27 acetylation significantly change. By combining transcriptomics, epigenomics, chromatin accessibility, and orthologous gene analyses with other unicellular and multicellular organisms, we identify 52 conserved genes, which are specifically accessible and expressed during multicellular states. We validated that four of these genes, including the H3K27 deacetylase hdaD, are necessary and that an SMC-like gene, smcl1, is sufficient for multicellularity in Dictyostelium.
CONCLUSIONS: These results highlight the importance of epigenetics in reorganizing chromatin architecture to facilitate multicellularity in Dictyostelium discoideum and raise exciting possibilities about the role of epigenetics in the evolution of multicellularity more broadly.

Keywords

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Grants

  1. DP2 AG067490/NIA NIH HHS
  2. R00 AG043550/NIA NIH HHS
  3. R01 GM110174/NIGMS NIH HHS
  4. DP2 AG055947/NIA NIH HHS
  5. T32 CA009140/NCI NIH HHS
  6. K99 AG064042/NIA NIH HHS

MeSH Term

Acetylation
Animals
Caenorhabditis elegans
Chromatin
Dictyostelium
Epigenesis, Genetic
Gene Expression Profiling
Histones
Methylation
Schizosaccharomyces
Transcription Factors

Chemicals

Chromatin
Histones
Transcription Factors