Transcriptionally active chromatin is marked by tri-methylation of histone H3 at lysine 4 (H3K4me3) located after first exons and around transcription start sites. This epigenetic mark is typically restricted to narrow regions at the 5`end of the gene body, though a small subset of genes have a broad H3K4me3 domain which extensively covers the coding region. Although most studies focus on the H3K4me3 mark, the broad H3K4me3 domain is associated with a plethora of histone modifications (e.g., H3 acetylated at K27) and is therein termed broad epigenetic domain. Genes marked with the broad epigenetic domain are involved in cell identity and essential cell functions and have clinical potential as biomarkers for patient stratification. Reducing expression of genes with the broad epigenetic domain may increase the metastatic potential of cancer cells. Enhancers and super-enhancers interact with the broad epigenetic domain marked genes forming a hub of interactions involving nucleosome-depleted regions. Together, the regulatory elements coalesce with transcription factors, chromatin modifying/remodeling enzymes, coactivators, and the Mediator and/or Integrator complex into a transcription factory which may be analogous to a liquid–liquid phase-separated condensate. The broad epigenetic domain has a dynamic chromatin structure which supports frequent transcription bursts. In this review, we present the current knowledge of broad epigenetic domains.
Bibliographical noteFunding Information:
Research was supported by grant from Natural Sciences and Engineering Research Council of Canada (RGPIN-2017-05927) and CancerCare Manitoba Foundation (761020318) to JRD. Additional funding was provided by the National Institutes of Health, USA (AR049069), to AJvW, and ANID/CONICYT - FONDECYT de Iniciación 11190998 to GN.
We acknowledge that the CancerCare Manitoba Research Institute and the University of Manitoba campuses are located on original lands of Anishinaabeg, Cree, Oji-Cree, Dakota and Dene peoples, and on the homeland of the M?tis Nation.
© 2021, The Author(s).
- Broad H3K4me3 domains
- Cell identity genes
- Histone modifications
- Tumor suppressor genes