Cullin4‐Ring ligase‐mediated degradation of an H3K9 methyltransferase compromises cell proliferation and fruit size in tomato

Summary Fruit development begins with cell division and expansion, which affects the final size and shape of the fruit. We previously showed tomato UV‐DAMAGED DNA BINDING PROTEIN 1 (SlDDB1) negatively regulates cell proliferation and organ size in an epigenetic manner, but the underlying molecular mechanism remains elusive. We identify two SlDDB1‐interacting proteins, SlMSI2 and SlSDG2, the orthologs of Arabidopsis MULTICOPY SUPPRESSOR OF IRA1 2 and SET DOMAIN GROUP 2, respectively, antagonistically controlling cell proliferation via the ubiquitin‐proteasome pathway in tomato. SlMSI2 encodes a WD40‐repeat protein and negatively involves cell proliferation and interacts with SlDDB1 and SlCUL4 to form the CRL4 SlMSI2 ligase complex, through which SlSDG2 is ubiquitinated for degradation. SlSDG2 codes for an H3K9 methyltransferase positively regulating cell proliferation and coordinates with a DNA methyltransferase SlCMT3a to negatively regulate expression of target genes, a subset of negative regulators involving cell division or cell cycle progression through concurrent methylation of H3K9 and DNA at the regulatory chromatin regions. The study reveals the mechanistic basis by which the CRL4 E3 ligase epigenetically regulates cell proliferation and fruit size and structure via ubiquitination‐mediated manipulation of the H3K9 methyltransferase. This work also presents novel targets for manipulating plant structure and size toward optimized agricultural outcomes.