MLL3/MLL4/COMPASS Family on Epigenetic Regulation of Enhancer Function and Cancer
Open accessAbstract
During development, precise spatiotemporal patterns of gene expression are coordinately controlled by cis-regulatory modules known as enhancers. Their crucial role in development helped spur numerous studies aiming to elucidate the functional properties of enhancers within their physiological and disease contexts. In recent years, the role of enhancer malfunction in tissue-specific tumorigenesis is increasingly investigated. Here, we direct our focus to two primary players in enhancer regulation and their role in cancer pathogenesis: MLL3 and MLL4, members of the COMPASS family of histone H3 lysine 4 (H3K4) methyltransferases, and their complex-specific subunit UTX, a histone H3 lysine 27 (H3K27) demethylase. We review the most recent evidence on the underlying roles of MLL3/MLL4 and UTX in cancer and highlight key outstanding questions to help drive future research and contribute to our fundamental understanding of cancer and facilitate identification of therapeutic opportunities.
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MLL3 and MLL4 catalyze H3K4 monomethylation and are recruited to target enhancers by TFs and pioneer factors.
“MLL3 and MLL4 catalyze H3K4 monomethylation and are recruited to target enhancers by TFs and pioneer factors37,38,59.”
From HNF4A guides the MLL4 complex to establish and maintain H3K4me1 at gene regulatory elements (2024) · cites this paper as [59]
The Drosophila section identifies MLL3/MLL4 as key H3K4 monomethyltransferases at enhancers. The section on models for malfunction discusses possible interactions with transcription factors, but says that identifying the key players that bring MLL3/MLL4 to enhancers remains an open question; it does not establish recruitment by TFs and pioneer factors. Page numbers were not available in our copy. (LLM, conf=0.89)
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“The epigenetic mark histone H3 lysine 4 (H3K4) monomethylation is particularly enriched on these regulatory elements, both active and inactive/poised (Heintzman et al. 2007, 2009; Smith and Shilatifard 2014).”
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Research works printed but not linked: 1
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The pancreatic cancer genome revisited
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- Authors
- Sze, C. C., & Shilatifard, A.
- Affiliations
- Northwestern University (US)
- Venue
- Cold Spring Harbor Perspectives in Medicine
- Publisher
- Cold Spring Harbor Laboratory
- Published
- 2016-09-16
- Volume
- 6
- Issue
- 11
- Pages
- a026427
- ISSN
- 2157-1422 (ISSN-L)
- PMC
- PMC5088509
- OpenAlex
- W2519986025
- Cited by
- 164
- References
- 12
- Citations by year
- 2026: 10 · 2025: 11 · 2024: 15 · 2023: 26 · 2022: 19 · 2021: 28 · 2020: 25 · 2019: 13 · 2018: 13 · 2017: 4
- Type
- posted content
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cold Spring Harbor Perspectives in Medicine (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institutes of Health
- National Cancer Institute (T32 CA09560, R35CA197569, T32CA009560)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
- Keywords
- MLL3, KMT2D, KDM6A, enhancer regulation, H3K4 methyltransferase, H3K27 demethylase, cancer epigenetics, histone modifications, cancer therapy targets
- MeSH terms
- Animals, Cell Transformation, Neoplastic, DNA-Binding Proteins, Enhancer Elements, Genetic, Histones, Humans, Methylation, Neoplasms, Histone-Lysine N-Methyltransferase, Protein Processing, Post-Translational, Gene Expression, Epigenesis, Genetic, Mice
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