SETD2-linking stem cell survival and transformation

• 来源期刊: 细胞研究（英文版）
• 年，卷（期）: 2018,（4）
• 页码范围: 393-394
• 页数: 2页
• 语种: 英文

摘要

SETD2 encodes a histone H3 lysine 36 (H3K36) methyltrans-ferase affected by mutations and deletions in a wide variety of cancers. Whether SETD2 loss alone can initiate tumorigenesis has not been established previously but in the present study, Zhang et al. identify that SETD2 deficiency eventually results in outgrowth of cells with a phenotype consistent with myelodysplastic syndromes and acute myeloid leukemia. Dynamic modifications of histones are important regulators of gene expression with H3K36me3 being tightly associated with transcriptionally active regions of chromatin and gene bodies.1 SETD2 is the sole H3K36 trimethyltransferase in eukaryotic cells and SETD2 has been ascribed to be involved in a number of biological processes mediated by diverse proteins with H3K36me3 reader domains (reviewed recently).2 This includes a role for SETD2 in DNA mismatch repair (through H3K36me3 binding of the protein hMS6), homologous recombination (mediated by LEDGF), DNA methylation (through H3K36me3 binding of DNMT3B), and nucleosome reorganization (through binding of the FACT complex to H3K36me3). Moreover, SETD2 itself physically associates with the hyperphosphorylated C-terminal domain of RNA polymerase II(RNA pol II), an association thought to link H3K36 trimethylation to sites of active transcription. The association between SETD2 and transcription has been shown to provide an indirect role for SETD2 in regulating RNA splicing, which is performed in a cotranscriptional manner and influenced by RNA pol II elongation at certain loci.