A Histone Methylation Network Regulates Transgenerational Epigenetic Memory in C. elegans
Eric L. Greer,
Sara E. Beese-Sims,
Emily Brookes,
Ruggero Spadafora,
Yun Zhu,
Scott B. Rothbart,
David Aristizábal-Corrales,
Shuzhen Chen,
Aimee I. Badeaux,
Qiuye Jin,
Wei Wang,
Brian D. Strahl,
Monica P. Colaiácovo,
Yang Shi
Affiliations
Eric L. Greer
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Sara E. Beese-Sims
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Emily Brookes
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Ruggero Spadafora
Division of Newborn Medicine, Children’s Hospital Boston, 300 Longwood Avenue, Boston, MA 02115, USA
Yun Zhu
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
Scott B. Rothbart
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
David Aristizábal-Corrales
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Shuzhen Chen
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Aimee I. Badeaux
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Qiuye Jin
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
Wei Wang
Department of Chemistry and Biochemistry, University of California, San Diego, La Jolla, CA 92093, USA
Brian D. Strahl
Department of Biochemistry and Biophysics, Lineberger Comprehensive Cancer Center, The University of North Carolina at Chapel Hill School of Medicine, Chapel Hill, NC 27599, USA
Monica P. Colaiácovo
Department of Genetics, Harvard Medical School, Boston, MA 02115, USA
Yang Shi
Department of Cell Biology, Harvard Medical School, Boston, MA 02115, USA
How epigenetic information is transmitted from generation to generation remains largely unknown. Deletion of the C. elegans histone H3 lysine 4 dimethyl (H3K4me2) demethylase spr-5 leads to inherited accumulation of the euchromatic H3K4me2 mark and progressive decline in fertility. Here, we identified multiple chromatin-modifying factors, including H3K4me1/me2 and H3K9me3 methyltransferases, an H3K9me3 demethylase, and an H3K9me reader, which either suppress or accelerate the progressive transgenerational phenotypes of spr-5 mutant worms. Our findings uncover a network of chromatin regulators that control the transgenerational flow of epigenetic information and suggest that the balance between euchromatic H3K4 and heterochromatic H3K9 methylation regulates transgenerational effects on fertility.
