GSE193075
H3K56 deacetylation and H2A.Z deposition are required for aberrant heterochromatin spreading
Crucial mechanisms are required to restrict self-propagating heterochromatin spreading within defined boundaries and prevent euchromatic gene silencing. In the filamentous fungus Neurospora crassa, the JmjC domain protein DNA METHYLATION MODULATOR-1 (DMM-1) prevents aberrant spreading of heterochromatin, but the molecular details remain unknown. Here, we revealed that DMM-1 is highly enriched in a well-defined 5-kb heterochromatin domain and constrained its aberrant spreading. Interestingly, aberrant spreading of the 5-kb heterochromatin domain observed in the dmm-1KO strain is accompanied by the sharp deposition of histone variant H2A.Z, and deletion of H2A.Z abolishes aberrant spreading of the 5-kb heterochromatin domain into adjacent euchromatin. Furthermore, lysine 56 of histone H3 is deacetylated at the expanded heterochromatin regions, and mimicking H3K56 acetylation with an H3K56Q mutation effectively blocks H2A.Z-mediated aberrant spreading of the 5-kb heterochromatin domain. More importantly, genome-wide analyses demonstrated the general roles of H3K56 deacetylation and H2A.Z deposition in aberrant spreading of heterochromatin.  Altogether, our results illustrate a previously unappreciated regulatory process that mediates aberrant heterochromatin spreading. Overall design: Dissectingthe molecular mechanisms of ectopic heterochromatin spreading in N. crassa.