SETD2-H3K36ME3: an important bridge between the environment and tumors

Abstract

Epigenetic regulation plays an important role in the occurrence, development and treatment of tumors. The histone methyltransferase SET-domain-containing 2 (SETD2) plays a key role in mammalian epigenetic regulation by catalyzing histone methylation and interacting with RNA polymerase II to mediate transcription elongation and mismatch repair. As an important bridge between the environment and tumors, SETD2-H3K36me3 plays an important role in the occurrence and development of tumors. Many tumors, including renal cancer, gastric cancer, lung cancer, are closely related to SETD2 gene mutations. As a key component of common tumor suppressor mechanisms, SETD2-H3K36me3is an important target for clinical disease diagnosis and treatment. Here, we reviewed the structure and function of the SETD2 and how SETD2-H3K36me3 functions as a bridge between the environment and tumors to provide an in-depth understanding of its role in the occurrence and development of various tumors, which is of great significance for future disease diagnosis and treatment.

Massively parallel interrogation of human functional variants modulating cancer immunosurveillance

“…Further analysis revealed that patients responding to ICB therapy (partial response and complete response: PR/CR) exhibited higher SETD2_Y1666C-mutation signature compared with non-response groups (progressive disease and stable disease: PD/SD) (Figure 7F), and the mutation signature also showed a positive correlation with progression-free survival (Figure 7G). Interestingly, recent studies also found that patients with different cancer types that harboring SETD2 deleterious mutations showed improved response to ICB therapy (He et al, 2023; Lu et al, 2021). Collectively, these findings firstly demonstrated the mechanisms of SETD2_Y1666C mutation in modulating immune surveillance and further supported the notion that the mutation is relevant to a better response to ICB treatment in clinical trials.…”

Genomic context-dependent histone H3K36 methylation by threeDrosophilamethyltransferases and implications for dedicated chromatin readers

“…Although K36 methylation is generally considered as an active mark, it is relevant for silencing by DNA methylation (13,14) and for silencing at facultative heterochromatin by H3K27me3 (15,16). In addition, K36me3 has been linked to genome stability (for review, see (70)) and HMTs establishing H3K36 methylation as well as K36me readers have been linked to cancer (71–73).…”

Genomic context-dependent histone H3K36 methylation by three Drosophila methyltransferases and implications for dedicated chromatin readers

“…Although K36 methylation is generally considered as an active mark, it is relevant for silencing by DNA methylation ( 13 , 14 ) and for silencing at facultative heterochromatin by H3K27me3 ( 15 , 16 ). In addition, K36me3 has been linked to genome stability (for review, see ( 76 )) and HMTs establishing H3K36 methylation as well as K36me readers have been linked to cancer ( 77–79 ).…”