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Broad H3K4me3 domains: Maintaining cellular identity and their implication in super-enhancer hijacking

Lookup NU author(s): Dan Kent, Dr Letizia MarchettiORCiD, Dr Aneta MikulasovaORCiD, Dr Lisa RussellORCiD, Dr Daniel Rico RodriguezORCiD

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This work is licensed under a Creative Commons Attribution 4.0 International License (CC BY 4.0).

Abstract

© 2023 The Authors. BioEssays published by Wiley Periodicals LLC. The human and mouse genomes are complex from a genomic standpoint. Each cell has the same genomic sequence, yet a wide array of cell types exists due to the presence of a plethora of regulatory elements in the non-coding genome. Recent advances in epigenomic profiling have uncovered non-coding gene proximal promoters and distal enhancers of transcription genome-wide. Extension of promoter-associated H3K4me3 histone mark across the gene body, known as a broad H3K4me3 domain (H3K4me3-BD), is a signature of constitutive expression of cell-type-specific regulation and of tumour suppressor genes in healthy cells. Recently, it has been discovered that the presence of H3K4me3-BDs over oncogenes is a cancer-specific feature associated with their dysregulated gene expression and tumourigenesis. Moreover, it has been shown that the hijacking of clusters of enhancers, known as super-enhancers (SE), by proto-oncogenes results in the presence of H3K4me3-BDs over the gene body. Therefore, H3K4me3-BDs and SE crosstalk in healthy and cancer cells therefore represents an important mechanism to identify future treatments for patients with SE driven cancers.

Publication metadata

Author(s): Kent D, Marchetti L, Mikulasova A, Russell LJ, Rico D

Publication type: Review

Publication status: Published

Journal: BioEssays

Year: 2023

Volume: 45

Issue: 10

Print publication date: 01/10/2023

Online publication date: 23/06/2023

Acceptance date: 30/05/2023

ISSN (print): 0265-9247

ISSN (electronic): 1521-1878

Publisher: John Wiley and Sons Inc

URL: https://doi.org/10.1002/bies.202200239

DOI: 10.1002/bies.202200239

PubMed id: 37350339

Data Access Statement: Data sharing is not applicable to this article as no new data were created or analysed in this review.

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