Broad domains of histone H3 lysine 4 trimethylation in transcriptional regulation and disease

Shinae Park, Go Woon Kim, So Hee Kwon, Jung Shin Lee

Research output: Contribution to journalReview articlepeer-review

34 Citations (Scopus)


Histone modifications affect transcription by changing the chromatin structure. In particular, histone H3 lysine 4 trimethylation (H3K4me3) is one of the most recognized epigenetic marks of active transcription. While many studies have provided evidence of the correlation between H3K4me3 and active transcription, details regarding the mechanism involved remain unclear. The first study on the broad H3K4me3 domain was reported in 2014; subsequently, the function of this domain has been studied in various cell types. In this review, we summarized the recent studies on the role of the broad H3K4me3 domain in transcription, development, memory formation, and several diseases, including cancer and autoimmune diseases. The broadest H3K4me3 domains are associated with increased transcriptional precision of cell-type-specific genes related to cell identity and other essential functions. The broad H3K4me3 domain regulates maternal zygotic activation in early mammalian development. In systemic autoimmune diseases, high expression of immune-responsive genes requires the presence of the broad H3K4me3 domain in the promoter-proximal regions. Transcriptional repression of tumor-suppressor genes is associated with the shortening of the broad H3K4me3 domains in cancer cells. Additionally, the broad H3K4me3 domain interacts with the super-enhancer to regulate cancer-associated genes. During memory formation, H3K4me3 breadth is regulated in the hippocampus CA1 neurons. Taken together, these findings indicate that H3K4me3 breadth is essential for the regulation of the transcriptional output across multiple cell types.

Original languageEnglish
Pages (from-to)2891-2902
Number of pages12
JournalFEBS Journal
Issue number14
Publication statusPublished - 2020 Jul 1

Bibliographical note

Funding Information:
This work was supported by the National Research Foundation of Korea grants (No. NRF‐013R1A1A3008065, NRF‐2015R1A4A1041105, NRF‐2015R1D1A1A02061743, and NRF‐2018R1D1A1A02048280).

Publisher Copyright:
© 2020 Federation of European Biochemical Societies

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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