The histone chaperone FACT facilitates heterochromatin spreading by regulating histone turnover and H3K9 methylation states
Magdalena Murawska,
R.A. Greenstein,
Tamas Schauer,
Karl C.F. Olsen,
Henry Ng,
Andreas G. Ladurner,
Bassem Al-Sady,
Sigurd Braun
Affiliations
Magdalena Murawska
Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; Corresponding author
R.A. Greenstein
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA; TETRAD Graduate Program, University of California, San Francisco, CA 94143, USA
Tamas Schauer
Bioinformatics Unit, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany
Karl C.F. Olsen
Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany
Henry Ng
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA; TETRAD Graduate Program, University of California, San Francisco, CA 94143, USA
Andreas G. Ladurner
Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany
Bassem Al-Sady
Department of Microbiology and Immunology, University of California, San Francisco, CA 94143, USA; George Williams Hooper Research Foundation, University of California, San Francisco, CA 94143, USA; Corresponding author
Sigurd Braun
Physiological Chemistry, Biomedical Center, Faculty of Medicine, Ludwig-Maximilians-University Munich, 82152 Planegg-Martinsried, Germany; International Max Planck Research School for Molecular and Cellular Life Sciences, 82152 Planegg-Martinsried, Germany; Institute for Genetics, Justus-Liebig University Giessen, 35392 Giessen, Germany; Corresponding author
Summary: Heterochromatin formation requires three distinct steps: nucleation, self-propagation (spreading) along the chromosome, and faithful maintenance after each replication cycle. Impeding any of those steps induces heterochromatin defects and improper gene expression. The essential histone chaperone FACT (facilitates chromatin transcription) has been implicated in heterochromatin silencing, but the mechanisms by which FACT engages in this process remain opaque. Here, we pinpoint its function to the heterochromatin spreading process in fission yeast. FACT impairment reduces nucleation-distal H3K9me3 and HP1/Swi6 accumulation at subtelomeres and derepresses genes in the vicinity of heterochromatin boundaries. FACT promotes spreading by repressing heterochromatic histone turnover, which is crucial for the H3K9me2 to me3 transition that enables spreading. FACT mutant spreading defects are suppressed by removal of the H3K9 methylation antagonist Epe1. Together, our study identifies FACT as a histone chaperone that promotes heterochromatin spreading and lends support to the model that regulated histone turnover controls the propagation of repressive methylation marks.
