MLL3 suppresses tumorigenesis through regulating TNS3 enhancer activity.
Jun-Yi ZhengChen-Yu WangChuan GaoQiong XiaoCheng-Wei HuangMin WuLian-Yun LiPublished in: Cell death & disease (2021)
MLL3 is a histone H3K4 methyltransferase that is frequently mutated in cancer, but the underlying molecular mechanisms remain elusive. Here, we found that MLL3 depletion by CRISPR/sgRNA significantly enhanced cell migration, but did not elevate the proliferation rate of cancer cells. Through RNA-Seq and ChIP-Seq approaches, we identified TNS3 as the potential target gene for MLL3. MLL3 depletion caused downregulation of H3K4me1 and H3K27ac on an enhancer ~ 7 kb ahead of TNS3. 3C assay indicated the identified enhancer interacts with TNS3 promoter and repression of enhancer activity by dCas9-KRAB system impaired TNS3 expression. Exogenous expression of TNS3 in MLL3 deficient cells completely blocked the enhanced cell migration phenotype. Taken together, our study revealed a novel mechanism for MLL3 in suppressing cancer, which may provide novel targets for diagnosis or drug development.
Keyphrases
- acute myeloid leukemia
- cell migration
- binding protein
- rna seq
- single cell
- transcription factor
- protein protein
- signaling pathway
- genome wide
- papillary thyroid
- poor prognosis
- dna methylation
- induced apoptosis
- high throughput
- gene expression
- crispr cas
- cell death
- childhood cancer
- lymph node metastasis
- young adults
- wild type