ASB7 is a negative regulator of H3K9me3 homeostasis.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 40440427.
- Also identified by DOI 10.1126/science.adq7408.
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Abstract
The maintenance of histone H3 lysine 9 trimethylation (H3K9me3) involves the recognition of preexisting modifications by heterochromatin protein 1 (HP1), which recruits the methyltransferase suppressor of variegation 3-9 homolog 1 (SUV39H1) to methylate the adjacent newly incorporated histones, establishing a positive feedback loop. However, how this positive feedback is restricted to maintain H3K9me3 homeostasis remains largely unknown. We performed an unbiased genome-scale CRISPR-Cas9 screen and identified CUL5<sup>ASB7</sup> 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.
Medical subject headings
- Cullin Proteins
- Heterochromatin
- Histones
- Lysine
- Methyltransferases
- Ubiquitin-Protein Ligases
- Ankyrins