RT Journal Article
SR Electronic
T1 The histone chaperone FACT facilitates heterochromatin spreading through regulation of histone turnover and H3K9 methylation states
JF bioRxiv
FD Cold Spring Harbor Laboratory
SP 2021.06.30.450523
DO 10.1101/2021.06.30.450523
A1 Murawska, Magdalena
A1 Greenstein, R. A.
A1 Schauer, Tamas
A1 Olsen, Karl C.F.
A1 Ng, Henry
A1 Ladurner, Andreas G.
A1 Al-Sady, Bassem
A1 Braun, Sigurd
YR 2021
UL http://biorxiv.org/content/early/2021/07/01/2021.06.30.450523.abstract
AB 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 has been implicated in heterochromatin silencing, however, the mechanisms by which FACT engages in this process remain opaque. Here, we pin-pointed its function to the heterochromatin spreading process. 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 via nucleosome stabilization. Together, our study identifies FACT as a histone chaperone that specifically promotes heterochromatin spreading and lends support to the model that regulated histone turnover controls the propagation of epigenetic marks.Competing Interest StatementThe authors declare a competing interest. A.G.L. is co-founder and CSO of Eisbach Bio GmbH.