biostudies-literatureZhang CNational Natural Science Foundation of ChinaNational Key Research and Development Program of China3852-3866https://www.ebi.ac.uk/biostudies/studies/S-EPMC9023284biostudies-literatureUnknown50(7)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 upstream of the cat-3 gene, hereby called 5H-cat-3 domain, to constrain aberrant heterochromatin spreading. Interestingly, aberrant spreading of the 5H-cat-3 domain observed in the dmm-1KO strain is accompanied by robust deposition of histone variant H2A.Z, and deletion of H2A.Z abolishes aberrant spreading of the 5H-cat-3 domain into adjacent euchromatin.Nucleic acids researchH3K56 deacetylation and H2A.Z deposition are required for aberrant heterochromatin spreading.PMC90232842018YFA09005003187125431771383Tian YSong SZhang LZhang CDang YHe QfalseH3K56 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 upstream of the cat-3 gene, hereby called 5H-cat-3 domain, to constrain aberrant heterochromatin spreading. Interestingly, aberrant spreading of the 5H-cat-3 domain observed in the dmm-1KO strain is accompanied by robust deposition of histone variant H2A.Z, and deletion of H2A.Z abolishes aberrant spreading of the 5H-cat-3 domain into adjacent euchromatin.2022-01-01T00:00:00Z2022 Apr2026-05-30T15:27:01.689Z2025-04-04T10:02:28.259ZS-EPMC90232843533335410.1093/nar/gkac196