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Cited by 217Genomics and Chromatin DynamicsEpigenetics and DNA MethylationChromatin Remodeling and Cancer

Histone H3K4 monomethylation catalyzed by Trr and mammalian COMPASS-like proteins at enhancers is dispensable for development and viability

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Rickels, Ryan, Herz, Hans-Martin, Sze, Christie C, Cao, Kaixiang, Morgan, Marc A, Collings, Clayton K, Gause, Maria, Takahashi, Yoh-hei +11 more·2017·Nature Genetics
DOI 10.1038/ng.3965PMC PMC5663216
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Abstract

Histone H3 lysine 4 monomethylation (H3K4me1) is an evolutionarily conserved feature of enhancer chromatin catalyzed by the COMPASS-like methyltransferase family, which includes Trr in Drosophila melanogaster and MLL3 (encoded by KMT2C) and MLL4 (encoded by KMT2D) in mammals. Here we demonstrate that Drosophila embryos expressing catalytically deficient Trr eclose and develop to productive adulthood. Parallel experiments with a trr allele that augments enzyme product specificity show that conversion of H3K4me1 at enhancers to H3K4me2 and H3K4me3 is also compatible with life and results in minimal changes in gene expression. Similarly, loss of the catalytic SET domains of MLL3 and MLL4 in mouse embryonic stem cells (mESCs) does not disrupt self-renewal. Drosophila embryos with trr alleles encoding catalytic mutants manifest subtle developmental abnormalities when subjected to temperature stress or altered cohesin levels. Collectively, our findings suggest that animal development can occur in the context of Trr or mammalian COMPASS-like proteins deficient in H3K4 monomethylation activity and point to a possible role for H3K4me1 on cis-regulatory elements in specific settings to fine-tune transcriptional regulation in response to environmental stress.

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  • Many enhancer-associated biochemical features may have nothing to do with the enhancers' mechanism of action.

    “Fourth, many enhancer-associated biochemical features may have nothing to do with the enhancers’ mechanism of action.”

    From Towards a comprehensive catalogue of validated and target-linked human enhancers (2020) · cites this paper as [81]

    The Abstract reports that changing the enhancer-associated H3K4me1 mark had minimal effects on gene expression and did not prevent development, supporting the idea that an associated feature need not be essential to enhancer function. But the paper studies this mark, not “many” biochemical features, and notes that H3K4me1 may still fine-tune regulation under stress. (LLM, conf=0.86)

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Research works printed but not linked: 32

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Authors
Rickels, R., Herz, H.-M., Sze, C. C., Cao, K., Morgan, M. A., Collings, C. K., Gause, M., Takahashi, Y.-H., Wang, L., Rendleman, E. J., Marshall, S. A., Krueger, A., Bartom, E. T., Piunti, A., Smith, E. R., Abshiru, N. A., Kelleher, N. L., Dorsett, D., & Shilatifard, A.
Affiliations
  • Northwestern University (US)
  • Stowers Institute for Medical Research (US)
  • Saint Louis University (US)
Corresponding author
Shilatifard, Ali
ORCID
Venue
Nature Genetics
Publisher
Springer Science and Business Media LLC
Published
2017-10-02
Volume
49
Issue
11
Pages
1647-1653
ISSN
  • 1061-4036 (ISSN-L)
  • 1546-1718
DOI
10.1038/ng.3965
PMC
PMC5663216
OpenAlex
W2761896392
Cited by
217
References
5
Citations by year
2026: 11 · 2025: 17 · 2024: 33 · 2023: 22 · 2022: 32 · 2021: 24 · 2020: 37 · 2019: 21 · 2018: 18 · 2017: 2
FWCI
8.49
Type
journal article
Language
en
Open access
Licence
www.springer.com/tdm (tdm)
Locations
  • Nature Genetics (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
  • National Cancer Institute (F31CA213928, R00CA181506, R50CA211428, R35CA197569, T32CA009560)
  • National Institute of General Medical Sciences (P41GM108569, R01GM108714)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Genomics and Chromatin Dynamics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Chromatin Remodeling and Cancer
Keywords
H3K4 monomethylation, H3K4me1, MLL3, KMT2D, Drosophila melanogaster, mouse embryonic stem cells, cohesin, temperature stress, cis-regulatory elements, transcriptional regulation
MeSH terms
Amino Acid Sequence, Animals, Chromatin, DNA-Binding Proteins, Drosophila melanogaster, Embryo, Nonmammalian, Enhancer Elements, Genetic, Histones, Larva, Methylation, Histone-Lysine N-Methyltransferase, Recombinant Proteins, Baculoviridae, Sequence Alignment, Sequence Homology, Amino Acid, Spodoptera, Gene Expression Regulation, Developmental, Drosophila Proteins, Mice, Sf9 Cells, CRISPR-Cas Systems

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