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We performed an unbiased genome-scale CRISPR-Cas9 screen and identified CUL5\n                    <jats:sup>ASB7<\/jats:sup>\n                    E3 ubiquitin ligase as a negative regulator of H3K9me3. ASB7 is recruited to heterochromatin by HP1 and promotes SUV39H1 degradation. During mitosis, cyclin-dependent kinase 1 (CDK1) phosphorylates ASB7, preventing its interaction with SUV39H1, leading to SUV39H1 stabilization and H3K9me3 restoration. Our findings reveal a dynamic circuit involving HP1, SUV39H1, and ASB7 that governs H3K9me3 homeostasis, ensuring faithful epigenetic inheritance and preventing excessive heterochromatin formation.\n                  <\/jats:p>","DOI":"10.1126\/science.adq7408","type":"journal-article","created":{"date-parts":[[2025,5,29]],"date-time":"2025-05-29T14:00:57Z","timestamp":1748527257000},"page":"309-316","update-policy":"https:\/\/doi.org\/10.34133\/aaas_crossmark","source":"Crossref","is-referenced-by-count":25,"title":["ASB7 is a negative regulator of H3K9me3 homeostasis"],"prefix":"10.1126","volume":"389","author":[{"ORCID":"https:\/\/orcid.org\/0000-0003-1092-3768","authenticated-orcid":true,"given":"Liwen","family":"Zhou","sequence":"first","affiliation":[{"name":"Sun Yat-sen University Cancer Center, State Key Laboratory of Oncology in South China, Guangdong Provincial Clinical Research Center for Cancer, Guangzhou, 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