Related Experiment Video

Updated: Jul 20, 2025

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors
06:07

Continuous Fluorescence-Based Endonuclease-Coupled DNA Methylation Assay to Screen for DNA Methyltransferase Inhibitors

Published on: August 5, 2022

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Histone methyltransferase KMT2D inhibits ENKTL carcinogenesis by epigenetically activating SGK1 and SOCS1

Yue-Hua Zhang1,2, Qing Tao1, Wen-Yan Zhang1

  • 1Department of Pathology, West China Hospital of Sichuan University, Chengdu, China.

Genes & Genomics
|July 31, 2023
PubMed
Abstract

Insights

Histone methyltransferase KMT2D acts as a tumor suppressor in extranodal natural killer/T cell lymphoma (ENKTL). It regulates cell proliferation and apoptosis by controlling the cell cycle and downstream genes SGK1 and SOCS1.

Area of Science:

  • Oncology
  • Epigenetics
  • Hematology

Background:

  • Epigenetic alterations are crucial in extranodal natural killer/T cell lymphoma (ENKTL) development.
  • The role of histone methyltransferase (HMT) KMT2D in ENKTL remains unclear despite its varied roles in other cancers.

Purpose of the Study:

  • To elucidate the function and mechanism of KMT2D in ENKTL.
  • To investigate KMT2D's impact on cell biological behavior and identify its downstream targets in ENKTL.

Main Methods:

  • Immunohistochemical staining of 112 ENKTL samples.
  • KMT2D knockdown cell line construction and analysis of cell behavior.
  • Chromatin immunoprecipitation sequencing (ChIP-seq) and ChIP-qPCR to identify downstream genes.

Main Results:

  • Low KMT2D expression correlated with reduced histone H3 lysine 4 mono- and trimethylation (H3K4me1/3).
  • KMT2D knockdown accelerated proliferation, decreased apoptosis, and increased S phase cells, linked to lower H3K4me1 levels.
  • ChIP-seq identified serum- and glucocorticoid-inducible kinase-1 (SGK1) and suppressor of cytokine signaling-1 (SOCS1) as KMT2D-regulated downstream genes.

Conclusions:

  • KMT2D functions as a tumor suppressor in ENKTL.
  • KMT2D regulates ENKTL cell cycle, proliferation, and apoptosis via H3K4me1 modification.
  • SGK1 and SOCS1 are identified as key downstream mediators of KMT2D function in ENKTL.
Keywords:
ENKTLH3K4me1Histone methylationKMT2D

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